Benzofuran compounds, compositions and methods for treatment and prophylaxis of hepatitis c viral infections and associated diseases

ABSTRACT

The present invention relates to novel benzofuran derivatives and analogs, as well as compositions containing the same and to the use thereof for the treatment or prophylaxis of viral infections and diseases associated therewith, particularly those viral infections and associated diseases caused by the hepatitis C virus.

This application claims the benefit of U.S. Provisional Application No.60/423,291, filed Nov. 1, 2002; U.S. Provisional Application No.60/461,077, filed Apr. 8, 2003; U.S. Provisional Application No.60/489,060 (Attorney Docket No. PCHC-0264P3-US), filed Jul. 23, 2003;and U.S. Provisional Application No. ______ (Attorney Docket No.PCHC-0264P4-US), filed Oct. 30, 2003. These applications are herebyincorporated by reference in their entirety.

FIELD OF THE INVENTION

The present invention relates to novel benzofuran derivatives andanalogs, as well as compositions containing the same and to the usethereof for the treatment or prophylaxis of viral infections anddiseases associated therewith, particularly those viral infections andassociated diseases caused by the hepatitis C virus.

BACKGROUND OF THE INVENTION

Hepatitis C is a common infection that can lead to chronic hepatitis,cirrhosis, liver failure, and hepatocellular carcinoma. Infection withthe hepatitis C virus (HCV) leads to chronic hepatitis in at least 85%of cases. It is the leading reason for liver transplantation, and isresponsible for at least 10,000 deaths annually in the United States(Hepatology, 1997, 26 (Suppl. 1), 2S-10S).

Interferon and interferon in combination with ribavirin are used in theU.S. for hepatitis due to HCV. These treatments are associated withimproved serum enzyme response in some patients. The remainder arenon-responsive to treatment. For responders, a sustained clinicalimprovement is seen in only a small percentage of patients; the majorityof patients relapse upon cessation of treatment. Thus, the effectivenessof therapy for chronic hepatitis C is variable and its cure rate remainslow. Moreover, therapy is often associated with considerable sideeffects.

New therapies and preventatives are clearly needed for infections anddiseases caused by the hepatitis C virus.

The hepatitis C virus is a member of the Flaviviridae family. The genomeof HCV is positive strand, single stranded linear RNA (Hepatology, 1997,26 (Suppl. 1), 11S-14S). HCV displays extensive genetic heterogeneity;at least six genotypes and more than 50 subtypes have been identified.

Following infection by HCV, the viral RNA is translated into apolyprotein. This approximately 3,000 residue polyprotein issubsequently cleaved into individual proteins by host peptidases, aswell as virally encoded proteases. The HCV genome encodes structuralproteins (required for virus assembly) and nonstructural proteins(required for replication). Some of the nonstructural proteins include:NS2, NS3, NS4A, NS4B, NS5A, and NS5B (J. General Virology, 2000, 81,1631-1648). NS5B is a RNA-dependent RNA polymerase that is essential forviral replication. In positive stranded RNA viruses, such as HCV, RNA isthe sole genetic material. Since mammalian host cells ordinarily lackRNA-dependent RNA polymerase activity, the positive stranded RNA virusesencode their own replicative polymerase (NS5B in the case of HCV), whichis essential for the production of virion progeny. The inhibition ofNS5B activity, therefore, provides an attractive target for HCV drugdesign.

SUMMARY OF THE INVENTION

In accordance with one aspect, the present invention provides compoundsand compositions for the treatment and prophylaxis of viral infections,as well as diseases associated with viral infections in living hosts.The compounds of the invention are of the following general formula:

wherein:

R₁ represents a radical selected from the group consisting of hydrogen,alkyl, halogen, and cyano;

R₂ represents a radical selected from the group consisting of hydrogen,a substituted or unsubstituted alkyl radical, a substituted orunsubstituted alkoxy group, hydroxy, cycloalkyl, cycloalkyloxy,polyfluoroalkyl, polyfluoroalkoxy, halogen, amino, monoalkylamino,dialkylamino, cyano, a substituted or unsubstituted benzyloxy group, anda substituted or unsubstituted heterocyclic radical;

R₃ represents a radical selected from the group consisting of hydrogen,a substituted or unsubstituted alkyl radical, a substituted orunsubstituted alkoxy group, alkenyl, halogen, hydroxy, polyfluoroalkyl,polyfluoroalkoxy, formyl, carboxyl, alkylcarbonyl, alkoxycarbonyl,hydroxyalkylcarbonyl, amino, a substituted or unsubstitutedmonoalkylamino, dialkylamino, cyano, amido, alkoxyamido, a substitutedor unsubstituted heteroarylamino, acetylsulfonylamino, ureido,carboxamide, sulfonamide, a substituted sulfonamide, a substituted orunsubstituted heterocyclosulfonyl, alkylthio, alkylsulfinyl,alkylsulfonyl, alkylsulfonic acid, a substituted or unsubstitutedheterocyclic radical, and —O(CH₂)—C(═O)—R₇;

R₄ represents a radical selected from the group consisting of hydrogen,alkyl, halogen, and alkoxy;

R₅ represents a radical selected from the group consisting of an alkyl(C₁-C₆) group, cycloalkyl, and cycloalkylalkyl;

R₆ represents a radical selected from the group consisting of asubstituted or unsubstituted aryl group and a substituted orunsubstituted heteroaryl group;

R₇ represents a radical selected from the group consisting ofdialkylamino, a substituted or unsubstituted arylamino, a substituted orunsubstituted heteroarylamino, and a substituted or unsubstituted arylgroup,

said monoalkylamino substituents being one or more radical(s)independently selected from the group consisting of cycloalkyl, hydroxy,alkoxy, and a substituted or unsubstituted heterocyclic radical;

said arylamino substituents and said heteroarylamino substituents beingone or more radical(s) independently selected from an alkyl group and analkoxycarbonyl;

said sulfonamide substituents being one or more radical(s) independentlyselected from the group consisting of alkenyl, cycloalkyl, alkoxy,hydroxy, halogen, polyfluoroalkyl, polyfluoroalkoxy, carboxyl,alkylcarbonyl, alkoxycarbonyl, carboxamide, a substituted orunsubstituted aryl group, and a substituted or unsubstitutedheterocyclic radical;

said heterocyclosulfonyl substituents being one or more radical(s)independently selected from the group consisting of alkoxy and hydroxy;

said alkyl radical substituents and said alkoxy group substituents beingone or more radical(s) independently selected from the group consistingof alkenyl, amino, monoalkylamino, dialkylamino, alkoxy, cycloalkyl,hydroxy, carboxyl, halogen, cyano, polyfluoroalkyl, polyfluoroalkoxy,sulfonamide, carboxamide, alkylsulfonyl, alkylcarbonyl, alkoxycarbonyl,mercapto, 2,2-dimethyl-4-oxo-4H-benzo[1,3]dioxinyl, a substituted orunsubstituted aryl group, and a substituted or unsubstitutedheterocyclic radical;

said heterocyclic radical substituents being one or more radical(s)independently selected from the group consisting of alkyl, amino, amido,monoalkylamino, cycloalkyl-alkylamino, dialkylamino, alkoxy,alkoxyalkyl, hydroxy, hydroxyalkyl, cycloalkyl, cycloalkylalkyl,carboxyl, carboxamide, halogen, haloalkyl, cyano, polyfluoroalkyl,polyfluoroalkoxy, alkylsulfonyl, alkylcarbonyl, cycloalkylcarbonyl,alkoxycarbonyl, mercapto, oxo, a substituted or unsubstituted arylgroup, arylalkyl, and a substituted or unsubstituted heteroaryl group;

said heteroaryl group substituents being one or more radical(s)independently selected from the group consisting of alkyl, amino,alkoxy, alkoxyalkyl, hydroxy, hydroxyalkyl, cycloalkyl, carboxyl,carboxamide, halogen, polyfluoroalkyl, polyfluoroalkoxy, alkylsulfonyl,mercapto, and oxo;

said benzyloxy group substituents being one or more radical(s)independently selected from the group consisting of alkyl, alkoxy,polyfluoroalkyl, polyfluoroalkoxy, hydroxy, carboxyl, alkoxycarbonyl,halogen, cyano, alkylsulfonyl, and phenyl;

said aryl group substituents being one or more radical(s) independentlyselected from the group consisting of alkyl, acetylenyl, alkoxy,hydroxy, halogen, polyfluoroalkyl, polyfluoroalkoxy, cyano, amino,monoalkylamino, dialkylamino, aminoalkyl, alkoxyalkoxy, amido,amidoalkyl, carboxyl, alkylsulfonyl, alkylcarbonyl, alkoxycarbonyl,mercapto, and a heterocyclic radical; and pharmaceutically acceptablesalts thereof;

with the proviso that said formula does not include the compoundsselected from the group consisting of5-methoxy-2-phenyl-benzofuran-3-carboxylic acid methylamide and5-hydroxy-2-phenyl-benzofuran-3-carboxylic acid methylamide.

The invention also relates to pharmaceutical compositions containing theantiviral compounds of Formula I and the corresponding methods of usefor treating and preventing infections caused by hepatitis C virus, aswell as the intermediate compounds and related methods of preparing theantiviral compounds described herein.

DETAILED DESCRIPTION OF THE INVENTION

In one aspect, the instant invention provides compounds of Formula I:

wherein R₁, R₂, R₃, R₄, R₅, and R₆ are as defined above.

In a second aspect, the instant invention provides compounds having theformula:

wherein:

R₁ represents a radical selected from the group consisting of hydrogen,alkyl, halogen, and cyano;

R₂ represents a radical selected from the group consisting of hydrogen,a substituted or unsubstituted alkyl radical, a substituted orunsubstituted alkoxy group, hydroxy, cycloalkyl, cycloalkyloxy,polyfluoroalkyl, polyfluoroalkoxy, halogen, amino, monoalkylamino,dialkylamino, cyano, a substituted or unsubstituted benzyloxy group, anda substituted or unsubstituted heterocyclic radical;

R₃, represents a radical selected from the group consisting of asubstituted or unsubstituted alkyl radical, a substituted orunsubstituted alkoxy group, alkenyl, halogen, hydroxy, polyfluoroalkyl,polyfluoroalkoxy, formyl, carboxyl, alkylcarbonyl, alkoxycarbonyl,hydroxyalkylcarbonyl, amino, a substituted or unsubstitutedmonoalkylamino, dialkylamino, cyano, amido, alkoxyamido, a substitutedor unsubstituted heteroarylamino, acetylsulfonylamino, ureido,carboxamide, sulfonamide, a substituted sulfonamide, a substituted orunsubstituted heterocyclosulfonyl, alkylthio, alkylsulfinyl,alkylsulfonyl, alkylsulfonic acid, a substituted or unsubstitutedheterocyclic radical, and —O(CH₂)—C(═O)—R₇;

R₄ represents a radical selected from the group consisting of hydrogen,alkyl, halogen, and alkoxy;

R₅ represents a radical selected from the group consisting of an alkyl(C₁-C₆) group, cycloalkyl, and cycloalkylalkyl;

R₆ represents a radical selected from the group consisting of asubstituted or unsubstituted aryl group and a substituted orunsubstituted heteroaryl group;

R₇ represents a radical selected from the group consisting ofdialkylamino, a substituted or unsubstituted arylamino, a substituted orunsubstituted heteroarylamino, and a substituted or unsubstituted arylgroup,

said monoalkylamino substituents being one or more radical(s)independently selected from the group consisting of cycloalkyl, hydroxy,alkoxy, and a substituted or unsubstituted heterocyclic radical;

said arylamino substituents and said heteroarylamino substituents beingone or more radical(s) independently selected from an alkyl group and analkoxycarbonyl;

said sulfonamide substituents being one or more radical(s) independentlyselected from the group consisting of alkenyl, cycloalkyl, alkoxy,hydroxy, halogen, polyfluoroalkyl, polyfluoroalkoxy, carboxyl,alkylcarbonyl, alkoxycarbonyl, carboxamide, a substituted orunsubstituted aryl group, and a substituted or unsubstitutedheterocyclic radical;

said heterocyclosulfonyl substituents being one or more radical(s)independently selected from the group consisting of alkoxy and hydroxy;

said alkyl radical substituents and said alkoxy group substituents beingone or more radical(s) independently selected from the group consistingof alkenyl, amino, monoalkylamino, dialkylamino, alkoxy, cycloalkyl,hydroxy, carboxyl, halogen, cyano, polyfluoroalkyl, polyfluoroalkoxy,sulfonamide, carboxamide, alkylsulfonyl, alkylcarbonyl, alkoxycarbonyl,mercapto, 2,2-dimethyl-4-oxo-4H-benzo[1,3]dioxinyl, a substituted orunsubstituted aryl group, and a substituted or unsubstitutedheterocyclic radical;

said heterocyclic radical substituents being one or more radical(s)independently selected from the group consisting of alkyl, amino, amido,monoalkylamino, cycloalkyl-alkylamino, dialkylamino, alkoxy,alkoxyalkyl, hydroxy, hydroxyalkyl, cycloalkyl, cycloalkylalkyl,carboxyl, carboxamide, halogen, haloalkyl, cyano, polyfluoroalkyl,polyfluoroalkoxy, alkylsulfonyl, alkylcarbonyl, cycloalkylcarbonyl,alkoxycarbonyl, mercapto, oxo, a substituted or unsubstituted arylgroup, arylalkyl, and a substituted or unsubstituted heteroaryl group;

said heteroaryl group substituents being one or more radical(s)independently selected from the group consisting of alkyl, amino,alkoxy, alkoxyalkyl, hydroxy, hydroxyalkyl, cycloalkyl, carboxyl,carboxamide, halogen, polyfluoroalkyl, polyfluoroalkoxy, alkylsulfonyl,mercapto, and oxo;

said benzyloxy group substituents being one or more radical(s)independently selected from the group consisting of alkyl, alkoxy,polyfluoroalkyl, polyfluoroalkoxy, hydroxy, carboxyl, alkoxycarbonyl,halogen, cyano, alkylsulfonyl, and phenyl;

said aryl group substituents being one or more radical(s) independentlyselected from the group consisting of alkyl, acetylenyl, alkoxy,hydroxy, halogen, polyfluoroalkyl, polyfluoroalkoxy, cyano, amino,monoalkylamino, dialkylamino, aminoalkyl, alkoxyalkoxy, amido,amidoalkyl, carboxyl, alkylsulfonyl, alkylcarbonyl, alkoxycarbonyl,mercapto, and a heterocyclic radical; and pharmaceutically acceptablesalts thereof.

In a third aspect, the instant invention provides compounds of theformula:

wherein:

R₁ represents a radical selected from the group consisting of hydrogen,alkyl, halogen, and cyano;

R₂ represents a radical selected from the group consisting of hydrogen,a substituted or unsubstituted alkyl radical, a substituted orunsubstituted alkoxy group, hydroxy, cycloalkyl, cycloalkyloxy,polyfluoroalkyl, polyfluoroalkoxy, halogen, amino, monoalkylamino,dialkylamino, cyano, a substituted or unsubstituted benzyloxy group, anda substituted or unsubstituted heterocyclic radical;

R₃ represents a radical selected from the group consisting of hydrogen,a substituted or unsubstituted alkyl radical, a substituted orunsubstituted alkoxy group, alkenyl, halogen, hydroxy, polyfluoroalkyl,polyfluoroalkoxy, formyl, carboxyl, alkylcarbonyl, alkoxycarbonyl,hydroxyalkylcarbonyl, amino, a substituted or unsubstitutedmonoalkylamino, dialkylamino, cyano, amido, alkoxyamido, a substitutedor unsubstituted heteroarylamino, acetylsulfonylamino, ureido,carboxamide, sulfonamide, a substituted sulfonamide, a substituted orunsubstituted heterocyclosulfonyl, alkylthio, alkylsulfinyl,alkylsulfonyl, alkylsulfonic acid, a substituted or unsubstitutedheterocyclic radical, and —O(CH₂)—C(═O)—R₇;

R₄ represents a radical selected from the group consisting of hydrogen,alkyl, halogen, and alkoxy;

R₅ represents a radical selected from the group consisting of an alkyl(C₁-C₆) group, cycloalkyl, and cycloalkylalkyl;

R_(6a) represents a radical selected from the group consisting of asubstituted aryl group and a substituted or unsubstituted heteroarylgroup;

R₇ represents a radical selected from the group consisting ofdialkylamino, a substituted or unsubstituted arylamino, a substituted orunsubstituted heteroarylamino, and a substituted or unsubstituted arylgroup,

said monoalkylamino substituents being one or more radical(s)independently selected from the group consisting of cycloalkyl, hydroxy,alkoxy, and a substituted or unsubstituted heterocyclic radical;

said arylamino substituents and said heteroarylamino substituents beingone or more radical(s) independently selected from an alkyl group and analkoxycarbonyl;

said sulfonamide substituents being one or more radical(s) independentlyselected from the group consisting of alkenyl, cycloalkyl, alkoxy,hydroxy, halogen, polyfluoroalkyl, polyfluoroalkoxy, carboxyl,alkylcarbonyl, alkoxycarbonyl, carboxamide, a substituted orunsubstituted aryl group, and a substituted or unsubstitutedheterocyclic radical;

said heterocyclosulfonyl substituents being one or more radical(s)independently selected from the group consisting of alkoxy and hydroxy;

said alkyl radical substituents and said alkoxy group substituents beingone or more radical(s) independently selected from the group consistingof alkenyl, amino, monoalkylamino, dialkylamino, alkoxy, cycloalkyl,hydroxy, carboxyl, halogen, cyano, polyfluoroalkyl, polyfluoroalkoxy,sulfonamide, carboxamide, alkylsulfonyl, alkylcarbonyl, alkoxycarbonyl,mercapto, 2,2-dimethyl-4-oxo-4H-benzo[1,3]dioxinyl, a substituted orunsubstituted aryl group, and a substituted or unsubstitutedheterocyclic radical;

said heterocyclic radical substituents being one or more radical(s)independently selected from the group consisting of alkyl, amino, amido,monoalkylamino, cycloalkyl-alkylamino, dialkylamino, alkoxy,alkoxyalkyl, hydroxy, hydroxyalkyl, cycloalkyl, cycloalkylalkyl,carboxyl, carboxamide, halogen, haloalkyl, cyano, polyfluoroalkyl,polyfluoroalkoxy, alkylsulfonyl, alkylcarbonyl, cycloalkylcarbonyl,alkoxycarbonyl, mercapto, oxo, a substituted or unsubstituted arylgroup, arylalkyl, and a substituted or unsubstituted heteroaryl group;

said heteroaryl group substituents being one or more radical(s)independently selected from the group consisting of alkyl, amino,alkoxy, alkoxyalkyl, hydroxy, hydroxyalkyl, cycloalkyl, carboxyl,carboxamide, halogen, polyfluoroalkyl, polyfluoroalkoxy, alkylsulfonyl,mercapto, and oxo;

said benzyloxy group substituents being one or more radical(s)independently selected from the group consisting of alkyl, alkoxy,polyfluoroalkyl, polyfluoroalkoxy, hydroxy, carboxyl, alkoxycarbonyl,halogen, cyano, alkylsulfonyl, and phenyl;

said aryl group substituents being one or more radical(s) independentlyselected from the group consisting of alkyl, acetylenyl, alkoxy,hydroxy, halogen, polyfluoroalkyl, polyfluoroalkoxy, cyano, amino,monoalkylamino, dialkylamino, aminoalkyl, alkoxyalkoxy, amido,amidoalkyl, carboxyl, alkylsulfonyl, alkylcarbonyl, alkoxycarbonyl,mercapto, and a heterocyclic radical; and pharmaceutically acceptablesalts thereof.

In a fourth aspect, the instant invention provides compounds of theformula:

wherein:

R₁ represents a radical selected from the group consisting of hydrogen,methyl, and chloro;

R₂ represents a radical selected from the group consisting of hydrogen,methyl, ethyl, isopropyl, t-butyl, cyclopropyl, hydroxy, hydroxymethyl,methoxymethyl, methoxy, trifluoromethoxy, difluoromethoxy,cyclopropylmethoxy, carboxymethoxy, cyanomethoxy, cyano-methyl-methoxy,1-hydroxymethyl-cyclopropylmethoxy, carbamoylmethoxy,methylcarbamoylmethoxy, diethylcarbamoylmethoxy,(4-ethoxycarbonyl-phenylcarbamoyl)-methoxy, tert-butoxycarbonylmethoxy,ethoxy, 2-methoxy-ethoxy, 2-chloro-ethoxy, 2-carboxyethoxy,2,2,2-trifluoroethoxy, 1-(4-fluoro-phenyl)-ethoxy,2-(4-fluoro-phenyl)-2-oxo-ethoxy, 2-(4-methoxy-phenyl)-2-oxo-ethoxy,propoxy, isopropoxy, 2-oxo-propoxy, 2-hydroxy-propoxy,3-hydroxy-propoxy, 2-hydroxy-2-methyl-propoxy, 3-bromo-propoxy,3-ethoxy-propoxy, butoxy, 2-hydroxy-2-methyl-butoxy, cyclopentyloxy,allyloxy, cyano, chloro, fluoro, methanesulfonic acid, benzyloxy,2-phenylbenzyloxy, 2-difluoromethoxy-benzyloxy, 3-methoxy-benzyloxy,3-methoxycarbonyl-benzyloxy, 3-carboxy-benzyloxy, 3-cyano-benzyloxy,4-methoxy-benzyloxy, 4-fluoro-benzyloxy, 4-cyano-benzyloxy,4-methoxycarbonyl-benzyloxy, 4-carboxy-benzyloxy,4-carboxy-3-hydroxy-benzyloxy, 4-methanesulfonyl-benzyloxy,3,4-difluoro-benzyloxy, 3,5-dimethoxy-benzyloxy,2,2-dimethyl-4-oxo-4H-benzo[1,3]dioxin-5-ylmethoxy,2,2-dimethyl-4-oxo-4H-benzo[1,3]dioxin-7-ylmethoxy,2,2-dimethyl-4-oxo-4H-benzo[1,3]dioxin-6-ylmethoxy,3-chloromethyl-[1,2,4]thiadiazol-5-yloxy,5-chloro-[1,2,4]thiadiazol-3-ylmethoxy,5-chloro-[1,2,3]thiadiazol-4-ylmethoxy,5-p-tolyl-[1,3,4]oxadiazol-2-ylmethoxy,5-(3,5-dimethyl-isoxazol-4-yl)-[1,2,4]oxadiazol-3-ylmethoxy,5-(cyclopropylmethyl-amino)-[1,2,4]thiadiazol-3-ylmethoxy,5-tert-butyl-[1,2,4]oxadiazol-3-ylmethoxy,5-(4-methoxy-phenyl)-[1,2,4]oxadiazol-3-ylmethoxy,5-diethylamino-[1,2,4]thiadiazol-3-ylmethoxy,[1,3,4]thiadiazol-2-ylcarbamoylmethoxy, 3,5-dimethyl-isoxazol-4-yl,isoxazol-3-ylmethoxy, 3,5-dimethyl-isoxazol-4-ylmethoxy,5-methyl-isoxazol-3-ylmethoxy, thiazol-2-ylmethoxy, thiazol-4-ylmethoxy,2-methyl-thiazol-4-ylmethoxy, 1-thiazol-2-yl-ethoxy,thiazol-2-ylcarbamoylmethoxy,(4,5-dimethyl-thiazol-2-ylcarbamoyl)-methoxy,4-chloro-1-methyl-1H-pyrazol-3-ylmethoxy, 2-pyrazol-1-yl-ethoxy,2-(3,5-dimethyl-pyrazol-1-yl)-ethoxy,4-ethoxycarbonyl-thiazol-2-ylmethoxy, 4-carboxy-thiazol-2-ylmethoxy,5-amino-4H-[1,2,4]triazol-3-ylmethoxy, thiophen-2-yl, furan-2-yl,2-morpholin-4-yl-ethoxy, 3-piperidin-1-yl-propoxy,tetrahydro-furan-2-yl, 1-methyl-1H-tetrazol-5-ylmethoxy,1-methyl-1H-imidazol-2-ylmethoxy, 1-benzyl-1H-imidazol-2-ylmethoxy,3H-imidazol-4-ylmethoxy, pyridine-4-yl-methoxy,6-bromomethyl-pyridin-2-ylmethoxy, and2-(4-cyano-piperidin-1-yl)-ethoxy;

R₃ represents a radical selected from the group consisting of hydrogen,methyl, methoxy, hydroxy, hydroxymethyl, 1-hydroxy-ethyl,1-hydroxy-2-methyl-propyl, 1-hydroxy-1-methyl-ethyl, formyl, ureido,vinyl, bromo, chloro, cyano, acetyl, 2-hydroxy-acetyl, carboxy,azetidin-1-yl, carboxylic acid amide, amino, methylamino, dimethylamino,ethylamino, diethylamino, isopropylamino, tert-butylamino,ethyl-methyl-amino, 2-methoxy-ethylamino, cyclopropylmethyl-amino,2,3-dihydroxy-propylamino, 1-methylamino-ethyl, dimethylaminomethyl,1-amino-1-methyl-ethyl, 2-amino-1-hydroxy-1-methyl-ethyl, acetylamino,1-acetylamino-1-methyl-ethyl, (2-methoxy-ethyl)-methyl-amino,ethyl-(2-methoxy-acetyl)-amino, 3-chloro-propane-1-sulfonylamino,methanesulfonylamino, ethyl-methanesulfonyl-amino,isopropyl-methanesulfonyl-amino, isobutyl-methanesulfonyl-amino,cyclobutyl-methanesulfonyl-amino, cyclopentyl-methanesulfonyl-amino,cyclopropylmethyl-methanesulfonyl-amino,(2-hydroxy-ethyl)-methanesulfonyl-amino,(2-hydroxy-propyl)-methanesulfonyl-amino,(2-fluoro-ethyl)-methanesulfonyl-amino,2-(4-fluoro-phenyl)-2-hydroxy-ethyl]-methanesulfonyl-amino,(1-hydroxymethyl-cyclopropylmethyl)-methanesulfonyl-amino,(4-carboxy-benzyl)-methanesulfonyl-amino, allyl-methanesulfonyl-amino,acetyl-methanesulfonyl-amino, benzyl-methanesulfonyl-amino,carboxymethyl-methanesulfonyl-amino, methanesulfonylamino-methyl,1-methanesulfonylamino-1-methyl-ethyl, methanesulfonyl-methyl-amino,1-(methanesulfonyl-methyl-amino)-ethyl, methanesulfonyl-propyl-amino,methanesulfonyl-(2-methoxy-ethyl)-amino,methanesulfonyl-(2,2,2-trifluoro-ethyl)-amino,methanesulfonyl-(2-oxo-propyl)-amino,methanesulfonyl-(2-trifluoromethoxy-ethyl)-amino,methanesulfonyl-(4-methoxy-benzyl)-amino,methanesulfonyl-(4-methoxycarbonyl-benzyl)-amino,methanesulfonyl-methoxymethyl-amino,methanesulfonyl-methylcarbamoylmethyl-amino,(methanesulfonyl-methyl-amino)-methyl, sulfamoyl, methylsulfamoyl,dimethylsulfamoyl, ethylsulfamoyl, cyclopropylsulfamoyl,cyclobutylsulfamoyl, 3-methanesulfonyl-phenyl, 4-methanesulfonyl-phenyl,benzyloxy, 1H-pyrazol-4-yl, 2H-pyrazol-3-yl, 1-methyl-1H-pyrazol-3-yl,2-methyl-2H-pyrazol-3-yl, 5-methyl-1H-pyrazol-4-yl,5-methyl-2H-pyrazol-3-yl, 1,5-dimethyl-1H-pyrazol-3-yl,2,5-dimethyl-2H-pyrazol-3-yl, 2,5-dimethyl-2H-pyrazol-3-ylamino,3,5-dimethyl-1H-pyrazol-4-yl, 1,3,5-trimethyl-1H-pyrazol-4-yl,isoxazol-3-yl, 5-methyl-isoxazol-3-yl, 3-cyclopropyl-isoxazol-5-yl,5-cyclopropyl-isoxazol-3-yl, 3,5-dimethyl-isoxazol-4-yl,3,5-dimethyl-isoxazol-4-ylamino, 5-methoxymethyl-isoxazol-3-yl,5-ethoxymethyl-isoxazol-3-yl, 5-isopropoxymethyl-isoxazol-3-yl,5-hydroxymethyl-isoxazol-3-yl, 4-(2-hydroxy-ethyl)-isoxazol-3-yl,3-methoxymethyl-5-methyl-isoxazol-4-yl,5-methoxymethyl-3-methyl-isoxazol-4-yl,5-cyclopropyl-3-methoxymethyl-isoxazol-4-yl,3-cyclopropyl-5-methoxymethyl-isoxazol-4-yl,(3,5-dimethyl-isoxazol-4-ylmethyl)-methanesulfonyl-amino,3-metho-xymethyl-isoxazol-5-yl), 3-methyl-isoxazol-5-yl,methanesulfonyl-(5-methyl-isoxazol-3-ylmethyl)-amino, thiazol-2-yl,thiazol-5-yl, methanesulfonyl-thiazol-2-ylmethyl-amino,methanesulfonyl-thiazol-4-ylmethyl-amino,methanesulfonyl-(2-methyl-thiazol-4-ylmethyl)-amino,(4-carboxy-thiazol-2-ylmethyl)-methanesulfonyl-amino,(4-ethoxycarbonyl-thiazol-2-ylmethyl)-methanesulfonyl-amino,pyridin-3-yl, pyridin-4-yl, pyridin-4-ylamino, 6-fluoro-pyridin-3-yl,methanesulfonyl-pyridin-4-ylmethyl-amino,(6-bromomethyl-pyridin-2-ylmethyl)-methanesulfonyl-amino,pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidine-1-sulfonyl,3-hydroxy-pyrrolidin-1-yl, 3-hydroxy-pyrrolidine-1-sulfonyl,5-oxo-pyrrolidin-3-yl, 1-acetyl-pyrrolidin-2-yl,1-acetyl-pyrrolidin-3-yl, 1-carbamoyl-pyrrolidin-2-yl,1-methylcarbamoyl-pyrrolidin-2-yl,4-methylcarbamoyl-5-oxo-pyrrolidin-3-yl,1-cyclopropanecarbonyl-pyrrolidin-2-yl,1-methanesulfonyl-pyrrolidin-2-yl, 1-methanesulfonyl-pyrrolidin-3-yl,3-amino-pyrrolidin-1-yl, 3-methanesulfonyl-pyrrolidin-1-yl,1H-pyrrol-2-yl, 1H-pyrrol-3-yl,3-cyano-4-hydroxy-2-oxo-2,5-dihydro-pyrrol-1-ylmethyl, furan-2-yl,furan-3-yl, (furan-3-ylmethyl)-amino, tetrahydro-furan-3-yl,(tetrahydro-furan-2-ylmethyl)-amino, [1,3,4]oxadiazol-2-yl,[1,2,4]oxadiazol-3-yl, 5-methyl-[1,2,4]oxadiazol-3-yl,5-methyl-[1,3,4]oxadiazol-2-yl, 5-trifluoromethyl-[1,2,4]oxadiazol-3-yl,morpholin-4-yl, 2,6-dimethyl-morpholin-4-yl,2-morpholin-4-yl-ethylamino, morpholine-4-sulfonyl,methanesulfonyl-(2-morpholin-4-yl-ethyl)-amino, thiomorpholin-4-yl,thiomorpholine-4-sulfonyl, 1-oxo-thiomorpholin-4-yl,1,1-dioxido-isothiazolidin-2-yl, 2-oxo-oxazolidin-5-yl,5-methyl-2-oxo-oxazolidin-5-yl, oxazol-5-yl, 1H-imidazol-4-yl,1H-imidazol-2-yl, 2,5-dioxo-imidazolidin-4-yl,4-methyl-2,5-dioxo-imidazolidin-4-yl, pyrimidin-5-yl,2,5-dimethyl-2H-[1,2,4]triazol-3-yl, 2-dimethyl-2H-[1,2,4]triazol-3-yl,4H-[1,2,4]triazol-3-yl, 5-methyl-2H-[1,2,4]triazol-3-yl,1H-tetrazol-5-yl, 1-methyl-1H-tetrazol-5-ylmethoxy,methanesulfonyl-(1-methyl-1H-tetrazol-5-ylmethyl)-amino, piperidin-1-yl,4-fluoro-piperidin-1-yl, 4,4-difluoro-piperidin-1-yl,3-hydroxy-piperidin-1-yl, 4-hydroxy-piperidin-1-yl,4-hydroxy-piperidine-1-sulfonyl, 4-carbamoyl-piperazin-1-yl,4-methyl-piperazin-1-yl, and 5-chloro-[1,2,4]thiadiazol-3-ylmethyl;

R₄ represents a radical selected from the group consisting of hydrogenand methyl;

R₅ represents a radical selected from the group consisting of methyl,ethyl, isopropyl, and cyclopropyl; and

R₆ represents a radical selected from the group consisting of phenyl,4-methyl-phenyl, 4-ethyl-phenyl, 4-methoxy-phenyl, 4-hydroxy-phenyl,4-bromo-phenyl, 2-chloro-phenyl, 2-fluoro-phenyl, 4-fluoro-phenyl,2,4-difluoro-phenyl, 3,4-difluoro-phenyl, 4-bromo-3-fluoro-phenyl,3-chloro-4-fluoro-phenyl, 4-chloro-3-fluoro-phenyl,2,4,5-trifluoro-phenyl, 3-fluoro-4-methyl-phenyl,4-fluoro-3-methyl-phenyl, 4-fluoro-3-hydroxy-phenyl,2-ethoxy-4-fluoro-phenyl, 3-trifluoromethyl-phenyl,4-trifluoromethyl-phenyl, 4-cyano-phenyl, 4-amino-phenyl,4-(acetylamino-methyl)-phenyl, 4-morpholin-4-yl-phenyl,4-pyrrolidin-1-yl-phenyl, furan-2-yl, furan-3-yl, 3-methyl-furan-2-yl,thiophen-2-yl, 5-chloro-thiophen-2-yl, pyridin-4-yl, and pyridin-3-yl;

with the proviso that said formula does not include the compoundsselected from the group consisting of5-methoxy-2-phenyl-benzofuran-3-carboxylic acid methylamide and5-hydroxy-2-phenyl-benzofuran-3-carboxylic acid methylamide.

Preferred compounds of Formula I include the compounds wherein R₂ is—OCH₃ or —O(CH)(CH₃)₂, —CH₂CH₃, and

Other preferred compounds of Formula I include the compounds wherein R₅is methyl.

A preferred aspect of the invention includes the compound of Formula Iwherein the aryl group represented by R₆ is a substituted phenyl, saidphenyl substituents being one or more radical(s) independently selectedfrom the group consisting of fluoro, chloro, bromo, methoxy, and cyano.

Another preferred aspect of the invention includes the compound of theFormula Ic:

wherein Alk is an alkyl group and R₁, R₃, and R₄ are as defined above inreference to Formula I; and pharmaceutically acceptable salts thereof.

Preferred compounds of the invention include2-(4-fluoro-phenyl)-5-methoxy-6-morpholin-4-yl-benzofuran-3-carboxylicacid methylamide,2-(4-fluoro-phenyl)-5-isopropoxy-6-morpholin-4-yl-benzofuran-3-carboxylicacid methylamide,2-(4-fluoro-phenyl)-5-isopropoxy-6-methanesulfonylamino-benzofuran-3-carboxylicacid methylamide,2-(4-fluoro-phenyl)-5-isopropoxy-6-[(2-methoxy-ethyl)-methyl-amino]-benzofuran-3-carboxylicacid methylamide,5-benzyloxy-2-(4-fluoro-phenyl)-6-morpholin-4-yl-benzofuran-3-carboxylicacid methylamide,2-(4-fluoro-phenyl)-6-[(furan-3-ylmethyl)-amino]-5-isopropoxy-benzofuran-3-carboxylicacid methylamide,6-(3,5-dimethyl-isoxazol-4-yl)-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylicacid methylamide,5-cyclopropyl-2-(4-fluoro-phenyl)-6-[(2-hydroxy-ethyl)-methanesulfonyl-amino]-benzofuran-3-carboxylicacid methylamide,6-(3,5-dimethyl-isoxazol-4-yl)-2-(4-fluoro-phenyl)-5-(3-hydroxy-propoxy)-benzofuran-3-carboxylicacid methylamide,5-ethoxy-2-(4-fluoro-phenyl)-6-(methanesulfonyl-methyl-amino)-benzofuran-3-carboxylicacid methylamide,2-(4-fluoro-phenyl)-6-[(2-hydroxy-ethyl)-methanesulfonyl-amino]-5-methoxy-benzofuran-3-carboxylicacid methylamide,5-ethyl-2-(4-fluoro-phenyl)-6-[(2-hydroxy-ethyl)-methanesulfonyl-amino]-benzofuran-3-carboxylicacid methylamide,2-(4-fluoro-phenyl)-6-[4-(2-hydroxy-ethyl)-isoxazol-3-yl]-5-methoxy-benzofuran-3-carboxylicacid methylamide, and pharmaceutically acceptable salts thereof.

According to another aspect, the present invention providespharmaceutical compositions comprising one or more compounds of FormulaI in combination with a pharmaceutically acceptable carrier medium.Preferred pharmaceutical compositions comprise one or more compoundslisted in Table 1 below, and pharmaceutically acceptable salts thereof,in combination with a pharmaceutically acceptable carrier medium

In accordance with yet another aspect, the present invention providesmethods for the prophylaxis or treatment of hepatitis C infections anddiseases associated with such infections in a living host, for example,a mammal including a human, comprising the step of administering atherapeutically effective amount of the compounds Formula I to a hostsusceptible to, or suffering from such infection.

Another aspect of the invention provides methods for the prophylaxis ortreatment of hepatitis C infections and diseases associated with suchinfections in a living host, for example, a mammal including a human.This method comprises administering a therapeutically effective amountof a compound selected from the group consisting of5-methoxy-2-phenyl-benzofuran-3-carboxylic acid methylamide and5-hydroxy-2-phenyl-benzofuran-3-carboxylic acid methylamide to a hostsusceptible to, or suffering from such infection.

The compounds of Formula I above, their isomers and pharmaceuticallyacceptable salts exhibit antiviral activity. The compounds of theinvention are particularly effective against hepatitis C virus and areuseful in the prophylaxis and/or treatment of infections and diseasesassociated with this virus in living hosts.

In vitro studies (cell-based and biochemical) have been performed whichdemonstrate the usefulness of compounds described herein as antiviralagents. For example, antiviral activity of representative compounds wasevaluated in a human liver derived cell line containing an HCV replicon.Also, antiviral activity was measured by the inhibitory activity of thecompounds against the viral RdRp in an enzymological assay for RNAsynthesis.

As used herein, the term “compounds of the invention” means,collectively, the compounds of Formula I, pharmaceutically acceptablesalts thereof, and mixtures thereof. The compounds of the invention areidentified herein by their chemical structure and/or chemical name.

The term “alkyl” as used herein refers to straight or branched chainaliphatic hydrocarbon radicals of up to 10 carbon atoms, preferably upto 6 carbon atoms and more preferably 1 to 4 carbon atoms. Similarly,the term “alkyl” or any variation thereof, used in combination form toname substituents, such as alkoxy (—O-alkyl),cycloalkylalkyl(-alkyl-cycloalkyl), arylalkyl(-alkyl-aryl),hydroxyalkyl(-alkyl-OH), monoalkylamino (—NH-alkyl),aminoalkyl(-alkyl-NH₂), alkylthio (—S-alkyl), alkylsulfinyl(—S(═O)-alkyl), alkylsulfonyl (—S(O)₂-alkyl), alkylsulfonic acid(—O—S(O)₂-alkyl), or the like also refers to straight or branched chainaliphatic hydrocarbon radicals of up to 10 carbon atoms, preferably 1 to6 carbon atoms, and more preferably of 1 to 4 carbon atoms. Also “alk”in a structural formula herein denotes an alkyl group, unless divalencyis indicated, in which case the “alk” denotes the corresponding alkylenegroup(s). Additionally, the term “alkyl (C₁-C₆)” denotes an alkyl grouphaving one to six carbon atoms.

The term “alkenyl” as used herein refers to straight or branched chainaliphatic hydrocarbon radicals of 2 to 7 carbon atoms containing atleast one double bond. Such alkenyl moieties may exist in the E or Zconfigurations; the compounds of this invention include bothconfigurations. The term “alkynyl” as used herein refers to straight orbranched chain aliphatic hydrocarbon radicals containing 2 to 7 carbonatoms having at least one triple bond.

The term “phenyl” as used herein refers to a

group. A “substituted phenyl” refers to a phenyl group that issubstituted with the indicated substituents.

As used herein, the term “aryl”, when used as such, or in combinationform, for example “aralkyl,” refers to an aromatic carbocyclic group,having 6 to 10 carbon atoms including, without limitation, phenyl andnapthyl.

The term “heteroaryl,” as used herein, refers to a 5- or 6-memberedaromatic cyclic group having at least one carbon atom and one or moreoxygen, nitrogen or sulfur atoms in the ring, as for example furyl,thienyl, pyridyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl,1,2,3-triazolyl, 1,2,4-triazolyl, 1-3-oxathiolanly, thiadiazolyl,tetrazolyl, and the like.

As used herein, the term “cycloalkyl” refers to non-aromatic carbocylicgroups, having 3 to 7 carbon atoms, as for example cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl and the like.

The term “cycloalkyloxy,” as used herein, refers to a radical orsubstituent of the formula —O-cycloalkyl, wherein cycloalkyl is asdefined above.

The term “polyfluoroalkyl,” as used herein, refers to an alkyl radicalor substituent having one or more fluoro substituents and includesperfluoroalkyl groups. Examples include trifluoromethyl andtrifluoroethyl. The term “polyfluoroalkoxy,” as used herein, refers toan alkoxy radical or substituent having one or more fluoro substituentsand includes perfluoroalkoxy groups. Examples include trifluoromethoxyand trifluoroethoxy.

The term “heterocyclic,” as used herein, refers to an aromatic ornon-aromatic cyclic group having in the ring at least one carbon atomand one to four heteroatoms independently selected from oxygen, nitrogenor sulfur atoms. The point of attachment of heterocyclic radicals caneither be through a carbon atom or a heteroatom. Heterocyclic radicalspreferably have 3 to 10 members, and more preferably 4, 5, or 6 membersin the ring. Examples of heterocyclic radicals include azetidinyl,furyl, tetrahydrofuranyl, thienyl, pyridyl, pyrrolyl, pyrrolinyl,pyrrolidinyl, piperidinyl, piperazinyl, pyrimidinyl, oxazolyl,oxazolidinyl, thiazolyl, imidazolyl, imidazolidinyl, pyrazolyl,2-pyrazolinyl, isoxazolyl, isothiazolyl, morpholinyl, thiomorpholinyl,1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-oxadiazolyl,1,2,3-triazolyl, 1,2,4-triazolyl, 1-3-oxathiolanly, thiadiazolyl,tetrazolyl, and the like.

The term “amido,” as used herein, refers to a radical or substituent ofthe formula —NR″C(═O)R′″, wherein R″ and R′″ independently representhydrogen, alkyl, or cycloalkyl. Similarly, the term “amidoalkyl,” asused herein, refers to a radical or substituent of the formula-alkyl-NR″C(═O)R′″, wherein R″ and R′″ are as previously defined.

The term “alkoxyamido,” as used herein, refers to a radical orsubstituent of the formula —NR″C(═O)-alkyl-alkoxy, wherein R″, alkyl,and alkoxy are as previously defined.

The term “carboxamide,” as used herein, refers to a radical orsubstituent of the formula —C(═O)—NR″R′″, wherein R″ and R′″ are aspreviously defined.

The term “ureido,” as used herein, refers to a radical or substituent ofthe formula —NR′C(═O)—NR″R′″, wherein R′ represents hydrogen or alkyland R″ and R′″ are as previously defined.

The term “sulfonamide,” as used herein, refers to a radical orsubstituent of the formula —SO₂NR″R′″ or —NR″SO₂R′″, wherein R″ and R′″are as previously defined. A substituted sulfonamide, as used herein,refers to a radical or substituent of the formula —N(alkyl)-SO₂(alkyl)in which at least one alkyl group is further substituted with theindicated substituents.

The term “acetylsulfonylamino,” as used herein, refers to a radical orsubstituent of the formula —N(SO₂—R″)—(C(═O)CH₃), wherein R″ is aspreviously defined.

The term “heterocyclosulfonyl,” as used herein, refers to a radical orsubstituent of the formula —SO₂—HET, wherein HET is a heterocyclic groupas defined above. Preferred heterocyclosulfonyl groups includepyrrolidinylsulfonyl, piperidinylsulfonyl, morpholinylsulfonyl, andthiomorpholinylsulfonyl.

The term “arylamino,” as used herein, refers to a radical or substituentof the formula —N(R″)-aryl, wherein R″ and aryl are as previouslydefined. A substituted arylamino, as used herein, refers to an arylaminoradical or substituent in which the aryl group is further substitutedwith the indicated substituents.

The term “heteroarylamino,” as used herein, refers to a radical orsubstituent of the formula —N(R″)-heteroaryl, wherein R″ and heteroarylare as previously defined. A substituted heteroarylamino, as usedherein, refers to a heteroarylamino radical or substituent in which theheteroaryl group is further substituted with the indicated substituents.

A substituted monoalkylamino, as used herein, refers to a radical orsubstituent of the formula —NH-alkyl in which the alkyl group is furthersubstituted with the indicated substituents. Similarly, the term“cycloalkyl-alkylamino,” as used herein, refers to a monoalkylaminoradical or substituent, as defined above, in which the alkyl group isfurther substituted with a cycloalkyl group as defined above.

The term “carboxyl,” as used herein, refers to a radical or substituentof the formula —C(═O)OH.

The term “carbonyl”, whether used alone or with other terms, such as“alkoxycarbonyl”, denotes —C(═O)—.

The term “alkylcarbonyl,” as used herein, refers to a radical orsubstituent of the formula —C(═O)-alkyl, and includes, for example,methylcarbonyl, ethylcarbonyl, propylcarbonyl, butylcarbonyl, andpentylcarbonyl. Similarly, the term “cycloalkylcarbonyl,” as usedherein, refers to a radical or substituent of the formula—C(═O)-cycloalkyl.

The term “hydroxyalkylcarbonyl,” as used herein, refers to a compound ofthe formula —C(═O)-alkyl-OH.

The term “alkoxycarbonyl,” as used herein, refers to a radical orsubstituent —C(═O)—O-alkyl, and includes, for example, methoxycarbonyl,ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, and pentoxycarbonyl.

The term “formyl,” as used herein, refers to a radical or substituent ofthe formula —C(═O)—H.

The term “mercapto,” as used herein, refers to a radical or substituentof the formula —SH.

The term “benzyloxy,” as used herein, refers to a radical or substituentof the formula —OCH₂-phenyl. A substituted benzyloxy is a benzyloxy inwhich the phenyl group is further substituted with the indicatedsubstituents.

The term “hexanes,” as used herein, refers to a solvent mixture ofstraight and branched chain hexane hydrocarbons, wherein the solventmixture contains mostly n-hexane and some minor amounts of branchedhexanes.

The term “halogen,” as used herein, refers to a radical or substituentselected from the group consisting of chloro, bromo, iodo, and fluoro.

The term “haloalkyl,” as used herein, refers to an alkyl group asdefined above that is further substituted with a halogen, as definedabove.

The term “psig” refers to pounds per square inch gauge.

The term “HPLC,” as used herein, refers to high-performance liquidchromatography.

The term “TLC,” as used herein, refers to thin layer chromatography.

The term “tautomeric form” as used herein refers two or more isomericstructures formed by migration of a hydrogen atom.

The term “amino” as used herein refers to an —NH₂ group.

The term “2,2-dimethyl-4-oxo-4H-benzo[1,3]dioxinyl” as used hereinrefers to a radical or substituent of the formula:

The term “living host” as used herein refers to an organism that isliving and capable of being infected with a virus, such as the hepatitisC virus; for example, a mammal, which includes a human.

The compounds of the present invention and their isomeric forms andpharmaceutically acceptable salts thereof are also useful in treatingand preventing viral infections, in particular hepatitis C infection,and diseases in living hosts when used in combination with each other orwith other biologically active agents, including but not limited to thegroup consisting of interferon, a pegylated interferon, ribavirin,protease inhibitors, polymerase inhibitors, small interfering RNAcompounds, anti-sense compounds, nucleotide analogs, nucleoside analogs,immunoglobulins, immunomodulators, hepatoprotectants, anti-inflammatoryagents, antibiotics, antivirals, and anti-infective compounds. Suchcombination therapy may also comprise providing a compound of theinvention either concurrently or sequentially with other medicinalagents or potentiators, such as acyclovir, famicyclovir, valgancyclovirand related compounds, ribavirin and related compounds, amantadine andrelated compounds, various interferons such as, for example,interferon-alpha, interferon-beta, interferon-gamma and the like, aswell as alternative forms of interferons such as pegylated interferons.Additionally, combinations of, for example ribavirin and interferon, maybe administered as an additional combination for a multiple combinationtherapy with at least one of the compounds of the present invention.

The combination therapy can be sequential, that is the treatment withone agent first and then the second agent (for example, where eachtreatment comprises a different compound of the invention or where onetreatment comprises a compound of the invention and the other comprisesone or more biologically active agent), or it can be treatment with bothagents at the same time (concurrently). The sequential therapy can bewithin a reasonable time after the completion of the first therapybefore beginning the second therapy. The treatment with both agents atthe same time can be in the same daily dose or in separate doses. Thedosages for both concurrent and sequential combination therapy willdepend on absorption, distribution, metabolism, and excretion rates ofthe components of the combination therapy as well as other factors knownto one of skill in the art. Dosage values will also vary with theseverity of the condition to be alleviated. It is to be furtherunderstood that for any particular subject, specific dosage regimens andschedules may be adjusted over time according to the individual's needand the professional judgment of the person administering or supervisingthe administration of the combination therapy.

In a further embodiment, the compounds of the invention may be used forthe treatment of HCV in humans in combination therapy mode with otherinhibitors of the HCV polymerase.

In yet a further embodiment, the compounds of the present invention maybe used for the treatment of HCV in humans in combination therapy modewith other inhibitors of the HCV life cycle such as, for example,inhibitors of HCV cell attachment or virus entry, HCV translation, HCVRNA transcription or replication, HCV maturation, assembly or virusrelease, or inhibitors of HCV enzyme activities such as the HCVnucleotidyl transferase, helicase, protease or polymerase.

It is intended that combination therapies of the present inventioninclude any chemically compatible combination of a compound of thisinventive group with other compounds of the inventive group or othercompounds outside of the inventive group, as long as the combinationdoes not eliminate the anti-viral activity of the compound of thisinventive group or the anti-viral activity of the pharmaceuticalcomposition itself.

The term “interferon-alpha” as used herein means the family of highlyhomologous species-specific proteins that inhibit viral replication andcellular proliferation and modulate immune response. Typical suitableinterferon-alphas include, but are not limited to, recombinantinterferon alpha-2b such as INTRON-A INTERFERON available from ScheringCorporation, Kenilworth, N.J., recombinant interferon alpha-2a such asRoferon interferon available from Hoffman-La Roche, Nutley, N.J., arecombinant interferon alpha-2C, such as BEROFOR ALPHA 2 INTERFERONavailable from Boehringer Ingelheim Pharmaceutical, Inc., Ridgefield,Conn., interferon alpha-n1, a purified blend of natural alphainterferons such as SUMIFERON available from Sumitomo, Japan or asWellferon interferon alpha-n1 (INS) available from Glaxo-Wellcome Ltd.,London, Great Britain, or a consensus alpha interferon such as thosedescribed in U.S. Pat. Nos. 4,897,471 and 4,695,623 (the contents ofwhich are hereby incorporated by reference in their entireties,specifically examples 7, 8 or 9 thereof) and the specific productavailable from Amgen, Inc., Newbury Park, Calif., or interferon alpha-n3a mixture of natural interferons made by Interferon Sciences andavailable from the Purdue Frederick Co., Norwalk, Conn., under theALFERON trademark. The use of interferon alpha-2a or alpha 2b ispreferred. Since interferon alpha 2b, among all interferons, has thebroadest approval throughout the world for treating chronic hepatitis Cinfection, it is most preferred. The manufacture of interferon alpha 2bis described in U.S. Pat. No. 4,503,901.

The term “pegylated interferon” as used herein means polyethylene glycolmodified conjugates of interferon, preferably interferon alpha-2a andalpha-2b. The preferred polyethylene-glycol-interferon alpha-2bconjugate is PEG.sub.12000-interferon alpha 2b. The phrase“PEG.sub.12000-IFN alpha” as used herein means conjugates such as areprepared according to the methods of International Application No. WO95/13090 and containing urethane linkages between the interferonalpha-2a or alpha-2b amino groups and polyethylene glycol having anaverage molecular weight of 12000.

Compounds described herein are also useful in preventing or resolvingviral infections in cell, tissue or organ cultures and other in vitroapplications. For example, inclusion of compounds of the invention as asupplement in cell or tissue culture growth media and cell or tissueculture components will prevent viral infections or contaminations ofcultures not previously infected with viruses. Compounds described abovemay also be used to eliminate viruses from cultures or other biologicalmaterials infected or contaminated with viruses (for example, blood),after a suitable treatment period, under any number of treatmentconditions as determined by the skilled artisan.

The compounds of the invention can form useful salts with inorganic andorganic acids such as hydrochloric, sulfuric, acetic, lactic, or thelike and with inorganic or organic bases such as sodium or potassiumhydroxide, piperidine, ammonium hydroxide, or the like. Thepharmaceutically acceptable salts of the compounds of Formula I areprepared following procedures that are familiar to those skilled in theart. For example, sodium and potassium salts can be made by dissolvingan appropriate compound of the invention in ethanol and adding about 1.1equivalents of sodium hydroxide or potassium hydroxide, and allowingsalt formation. Examples of pharmaceutically acceptable salts are listedin Table 3, below.

The isomeric forms of the compounds of the invention include, withoutlimitation, the various isomers of the heterocyclic substituents thatmay be present therein. The chemical structures depicted herein andtherefore the compounds of the invention also encompass all of thecorresponding possible tautomeric forms. Such tautomers may, in certaininstances, be resolved into individual compounds by methods known tothose of skill in the art.

The compounds of the present invention are useful for treating HCV inliving hosts, for example, mammals including humans. When administeredto a living host the compounds can be used alone, or as a pharmaceuticalcomposition.

Pharmaceutical compositions comprising the compounds of the presentinvention, either alone or in combination with each other, offer atreatment against hepatitis C infection. The antiviral pharmaceuticalcompositions of the present invention comprise one or more of thecompound(s) of Formula I above, as the active ingredient in combinationwith a pharmaceutically acceptable carrier medium or auxiliary agent.

The composition may be prepared in various forms for administration,including tablets, caplets, pills or dragees, or can be filled insuitable containers, such as capsules, or, in the case of suspensions,filled into bottles. As used herein, “pharmaceutically acceptablecarrier medium” includes any and all solvents, diluents, or other liquidvehicle, dispersion or suspension aids, surface active agents, isotonicagents, thickening or emulsifying agents, preservatives, solid binders,lubricants and the like, as suited to the particular dosage formdesired. Remington's Pharmaceutical Sciences, Twentieth Edition, A. R.Gennaro (William and Wilkins, Baltimore, Md., 2000) discloses variouscarriers used in formulating pharmaceutical compositions and knowntechniques for the preparation thereof. Except insofar as anyconventional carrier medium is incompatible with the antiviral compoundsof the invention, such as by producing any undesirable biological effector otherwise interacting in a deleterious manner with any othercomponent(s) of the pharmaceutical composition, its use is contemplatedto be within the scope of this invention.

In the pharmaceutical compositions of the invention, the active agentmay be present in an amount of at least 0.5% and generally not more than90% by weight, based on the total weight of the composition, includingcarrier medium and/or auxiliary agent(s), if any. Preferably, theproportion of active agent varies between 5 to 50% by weight of thecomposition.

Pharmaceutical organic or inorganic solid or liquid carrier mediasuitable for enteral or parenteral administration can be used to make upthe composition. Gelatine, lactose, starch, magnesium stearate, talc,vegetable and animal fats and oils, gum, polyalkylene glycol, or otherknown medicament components may all be suitable as carrier media orexcipients.

The compounds of the invention may be administered using any amount andany route of administration effective for attenuating infectivity of thevirus. Thus, the expression “amount effective to attenuate infectivityof virus,” as used herein, refers to a nontoxic but sufficient amount ofthe antiviral agent to provide the desired prophylaxis and/or treatmentof viral infection. The exact amount required will vary from subject tosubject, depending on the species, age, and general condition of thesubject, the severity of the infection, the particular antiviral agent,its mode of administration, and the like.

The antiviral compounds are preferably formulated in dosage unit formfor ease of administration and uniformity of dosage. “Dosage unit form”as used herein refers to a physically discrete unit of antiviral agentappropriate for the patient to be treated. Each dosage should containthe quantity of active material calculated to produce the desiredtherapeutic effect either as such, or in association with the selectedpharmaceutical carrier medium and/or the supplemental active agent(s),if any. Typically, the antiviral compounds of the invention will beadministered in dosage units containing from about 2 mg to about 7000 mgof the antiviral agent by weight of the composition, with a range ofabout 10 mg to about 2000 mg being preferred.

The compounds may be administered orally, rectally, parenterally, suchas by intramuscular injection, subcutaneous injection, intravenousinfusion or the like, intracisternally, intravaginally,intraperitoneally, locally, such as by powders, ointments, or drops, orthe like, or by inhalation, such as by aerosol or the like, taking intoaccount the nature and severity of the infection being treated.Depending on the route of administration, the compounds of the inventionmay be administered at dosage levels of about 0.05 to about 100 mg/kg ofsubject body weight per day, one or more times a day, to obtain thedesired therapeutic effect.

The compounds of the invention will typically be administered from 1 to4 times a day so as to deliver the above-mentioned daily dosage.However, the exact regimen for administration of the compounds andcompositions described herein will necessarily be dependent on the needsof the individual host or patient being treated, the type of treatmentadministered and the judgment of the attending medical specialist.

In view of the inhibitory effect on viral RNA synthesis produced by thecompounds of the invention, it is anticipated that these compounds willbe useful not only for therapeutic treatment of virus infection, but forvirus infection prophylaxis, as well. The dosages may be essentially thesame, whether for treatment or prophylaxis of virus infection.

The following examples are provided to describe the invention in furtherdetail. These examples illustrate suitable methods of synthesis ofrepresentative compounds of this invention. However, the methods ofsynthesis are intended to illustrate and not to limit the invention tothose exemplified below. The starting materials for preparing thecompounds of the invention are either commercially available or can beconveniently prepared according to one of the examples set forth belowor otherwise using known chemistry procedures.

Example 1 Preparation of 2-furan-3-yl-5-methoxy-benzofuran-carboxylicacid methylamide

a. Preparation of compound 1(a)(2-furan-3-yl-5-hydroxy-benzofuran-3-carboxylic acid ethyl ester). In anoven dried 25 mL 3-neck flask under argon was dissolved ethylβ-oxo-3-furanpropionate (2.22 g, 12.2 mmol) in absolute ethanol (4 mL)with magnetic stirring. Zinc chloride (anhydrous, 1.66 g, 12.2 mmol) wasadded, and the reaction was stirred magnetically until homogenous (20minutes). Solid 1,4-benzoquinone (1.32 g, 12.2 mmol) was placed in aglass-wool insulated side-arm addition funnel atop the reaction flask (acotton plug was used), capped by a cold finger. The reaction was heatedin an oil bath until gently refluxing, with the hot ethanol slowlydissolving and dripping the 1,4-benzoquinone into the pot over a periodof 18 hours. The reaction was cooled to room temperature and treatedwith water (about 100 mL). After extraction with ethyl acetate (3×75mL), the organics were combined, dried with Na₂SO₄, and evaporated. Theresulting oil was purified by HPLC (silica gel, ethyl acetate/hexanes)to provide 1.42 g (43%) of the product as pale yellow crystals.

b. Preparation of compound 1(b)(2-furan-3-yl-5-methoxy-benzofuran-3-carboxylic acid ethyl ester). In anoven-dried 50 mL flask under argon was combined compound 1(a) (1.42 g,5.21 mmol), potassium carbonate (milled, 2.16 g, 15.6 mmol) andanhydrous acetonitrile (20 mL). Methyl iodide (3.25 mL, 52.2 mmol) wasadded to this mixture, and the reaction was heated to reflux for 18hours. The reaction was cooled to room temperature and filtered througha pad of Celite™ 503 (diatomaceous earth) before evaporation of thesolvent. The resulting solid was purified by HPLC (silica gel, ethylacetate/hexanes) to provide 1.37 g (92%) of the desired product as paleyellow crystals.

c. Preparation of compound 1(c)(2-furan-3-yl-5-methoxy-benzofuran-3-carboxylic acid). Compound 1(b)(1.37 g, 4.78 mmol) was combined with potassium hydroxide pellets (0.4g, 7.13 mmol) in 50% aqueous ethanol (35 mL) in a 50 mL flask. Themixture was refluxed overnight and cooled to room temperature.Evaporation of half of the solvent and acidification with 3M HClprecipitated a white solid that was filtered, washed with water, anddried under vacuum at 60° C. to provide 1.21 g (97%) of the desiredproduct.

d. Preparation of 2-furan-3-yl-5-methoxy-benzofuran-carboxylic acidmethylamide. Compound 1(c) (0.05 g, 0.19 mmol) was dissolved inanhydrous tetrahydrofuran (THF) (3 mL) in an oven-dried 10 mL flaskunder argon. 1,1′-Carbonyldiimidazole (0.05 g, 0.31 mmol) was added withmagnetic stirring, and the resulting mixture was gently heated to about50° C. for 30 minutes to drive off CO₂. Excess methylamine (2.0M in THF,2 mL) was added, and heating continued for 4 hours. The reaction wascooled to room temperature, and the solvent was evaporated yielding anoil, which was purified by HPLC (reverse-phase C18, acetonitrile/water).After lypholization, 0.021 g (39%) of the desired product was isolatedas a white solid.

Example 2 Preparation of2-phenyl-5-trifluoromethoxy-benzofuran-3-carboxylic acid methylamide

a. Preparation of compound 2(a)(5-hydroxy-2-phenyl-benzofuran-3-carboxylic acid ethyl ester). Theintermediate compound was prepared essentially according to the generalprocedure described in Example 1, step a above; however, ethylbenzoylacetate was used instead of ethyl β-oxo-3-furanpropionate.

b. Preparation of compound 2(b)(5-thiomethylthiocarbonyloxy-2-phenyl-benzofuran-3-carboxylic acid ethylester). In a 25 mL flask open to the atmosphere, tetrabutylammoniumhydrogen sulfate (0.06 g, 0.177 mmol) was added to 12M sodium hydroxide(5 mL) and carbon disulfide (5 mL) with magnetic stirring. Compound 2(a)(0.5 g, 1.77 mmol) and methyl iodide (0.12 mL, 1.93 mmol) were added,and the mixture was stirred vigorously for 1 hour at room temperature.The reaction mixture was poured into a separatory funnel, the organiclayer collected, and the aqueous layer washed with carbon disulfide(3×10 mL). The organics were combined, dried with sodium sulfate, andthe solvent was evaporated yielding an orange oil, which was purified byHPLC (silica gel, ethyl acetate/hexanes) to provide 0.42 g (63%) of thedesired product as a clear oil.

c. Preparation of compound 2(c)(2-phenyl-5-trifluoromethoxy-benzofuran-3-carboxylic acid ethyl ester).In a 25 mL flask under argon, HF/Pyridine (70%, 2.56 mL) was added to asuspension of 1,3-dibromo-5,5-dimethylhydantoin (0.96 g, 3.36 mmol) andcompound 2(b) (0.42 g, 1.13 mmol) in dichloromethane (10 mL) at −78° C.Once the addition was complete (20 minutes), the reaction wastransferred to an ice bath and stirred magnetically for 1 hour at 0° C.The reaction mixture was then poured into a solution of 50:50 saturatedaqueous NaHCO₃/NaHSO₃ (100 mL) and extracted into diethyl ether (3×40mL). The organics were dried with sodium sulfate, and the solvent wasevaporated. The crude product was purified by HPLC (reverse-phase C18,acetonitrile/water) to provide 0.12 g (30%) of the desired product as ayellow oil.

d. Preparation of 2-phenyl-5-trifluoromethoxy-benzofuran-3-carboxylicacid methylamide. The title compound was prepared essentially accordingto the procedure described in Example 1, steps c and d above; however,compound 2(c) was used in step c instead of compound 1(b).

Example 3 Preparation of2-(3,4-difluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acidmethylamide

a. Preparation of compound 3(a) (3-(3,4-difluoro-phenyl)-3-oxo-propionicacid ethyl ester). Ethyl malonate potassium salt (7.46 g, 43.8 mmol) andMgCl₂ (3.14 g, 33.0 mmol) were mixed in anhydrous THF (36 mL) andrefluxed for 4 hours. To a separate solution of 3,4-difluorobenzoic acid(5.22 g, 33.0 mmol) in anhydrous THF (36 mL) was added1,1′-carbonyldiimidazole (6.29 g, 38.8 mmol) in one portion, and themixture was heated for 30 minutes. The second solution was then added tothe MgCl₂ solution at room temperature. The reaction mixture was stirredovernight (16 hours) at room temperature. The reaction flask was cooledin an ice bath, and an HCl solution (10 mL of concentrated HCl and 20 mLof H₂O) was added. The resulting mixture was stirred at room temperaturefor 1 hour. Ethyl acetate was added to extract the product, and thecombined organic layers were washed with brine and water, dried overNa₂SO₄, and concentrated to give an oil residue. The crude product waspurified by a short flash column (silica gel, 10:90 ethylacetate/hexanes) to provide 7.0 g (93%) of the desired product as anoff-white oil product.

b. Preparation of compound 3(b)(2-(3,4-difluoro-phenyl)-5-hydroxy-benzofuran-3-carboxylic acid ethylester). Absolute ethanol (10 mL) was added to an oven-dried flaskcontaining anhydrous ZnCl₂ (2.98 g, 21.9 mmol, pre-dried in oven for 1hour) under argon. Compound 3(a) (5.0 g, 21.9 mmol) was then added tothe above clear solution. 1,4-Benzoquinone (2.37 g, 21.9 mmol) wasplaced in an addition funnel with a side arm (a pad of glass wool at thebottom of funnel), and a condenser was equipped on the top of theaddition funnel. The reaction mixture in the flask was slowly heated to105° C. in an oil bath. Ethanol slowly refluxed through the side arm ofthe addition funnel (wrapped with glass wool and aluminum foil), andthen slowly washed down the 1,4-benzoquinone overnight (18 hours). Thereaction mixture was cooled to room temperature, diluted with ethylacetate, washed with brine and water, and dried over Na₂SO₄. Afterconcentration, the residue was purified by flash column chromatography(silica gel, 5 to 10% ethyl acetate in hexanes) to provide 3.60 g (52%)of the desired product as a pale yellow solid.

c. Preparation of compound 3(c)(2-(3,4-difluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acid ethylester). Potassium carbonate (276 mg, 2.0 mmol) was added to compound3(b) (255 mg, 0.8 mmol) in acetonitrile (5 mL). The mixture was heatedto reflux for 30 minutes, than cooled to room temperature. Methyl iodide(249 μl, 4.0 mmol) was added, and the reaction mixture was stirredovernight. The mixture was diluted with water and extracted into ethylacetate. The organic layer was washed with brine and dried. The crudeproduct was purified by column chromatography (silica gel, 5:95 ethylacetate/hexanes) to provide 235 mg (88%) of product as a white solid.

d. Preparation of compound 3(d)(2-(3,4-difluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acid). Sodiumhydroxide (10N, 0.5 mL) was added to a hot solution of compound 3(c)(230 mg, 0.69 mmol) in absolute ethanol (8 mL). The reaction mixture washeated to 90° C. and stirred for 2 hours. After cooling to roomtemperature, the mixture was acidified with 10% HCl to pH 2. Theresulting suspension was extracted with ethyl acetate, dried over Na₂SO₄and concentrated to provide a white solid (210 mg) in quantitativeyield. The product was taken directly to the next step without furtherpurification.

e. Preparation of2-(3,4-difluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acidmethylamide. Methylamine (0.45 mL, 2.0M in THF) was added to a solutionof compound 3(d) (91 mg, 0.30 mmol) in anhydrous N,N-dimethylformamide(DMF) (5 mL) under argon, followed by the addition ofbenzotriazol-1-yloxytrispyrrolidinophosphonium hexafluorophosphate(PyBOP) (156 mg, 0.30 mmol). The resulting reaction mixture was stirredat room temperature for 2 hours, diluted with water, extracted withethyl acetate, dried and concentrated. The crude product was purified bychromatography (silica gel, 10:90 ethyl acetate/hexanes) to provide 72mg (76%) of the product as a white solid.

Example 4 Preparation of2-[4-(acetylamino-methyl)-phenyl]-5-isopropoxy-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 4(a) (3-(4-bromo-phenyl)-3-oxo-propionic acidethyl ester). A mixture of ethyl malonate potassium salt (5.63 g, 33.08mmol) and magnesium chloride (2.37 g, 24.87 mmol) was refluxed in THF(60 mL) under argon for 4 hours. In a second reaction vessel,1,1′-carbonyldiimidazole (4.76 g, 29.35 mmol) was added to a solution of4-bromobenzoic acid (5.0 g, 24.87 mmol) in THF (30 mL) under argon, andthe solution was gently refluxed for 30 minutes. Both reactions werecooled to room temperature, and the second solution was added drop wiseto the ethyl malonate/magnesium chloride mixture. The reaction wasstirred at room temperature for 16 hours. Concentrated hydrochloric acid(10 mL) and water (20 mL) were mixed in an addition funnel and addeddropwise to the reaction mixture over a 15-minute period. The organicsolvents were removed by rotary evaporation, and the product wasextracted several times with ethyl acetate. The organics were combined,washed with brine and concentrated. The product was purified by flashchromatography (silica gel, ethyl acetate/hexanes gradient) to provide6.07 g (90%) of the desired product as an orange oil.

b. Preparation of compound 4(b)(2-(4-bromo-phenyl)-5-hydroxy-benzofuran-3-carboxylic acid ethyl ester).An addition funnel, flask, stir bar and zinc chloride (3.02 g, 22.13mmol) were oven dried for an hour and cooled under argon. Compound 4(a)(6.0 g, 22.13 mmol) was dissolved in ethanol (11 mL) and added to theflask containing the zinc chloride. 1,4-Benzoquinone (2.39 g, 22.13mmol) was added through an addition funnel (wrapped with glass wool andaluminum foil and using a cotton plug). The reaction was heated to 105°C. in an oil bath, while regulating the amount of ethanol condensinginto the addition funnel to facilitate an 18-hour addition of the1,4-benzoquinone. When the 1,4-benzoquinone was consumed, the reactionwas cooled to room temperature, ethyl acetate was added, and the crudeproduct was washed with brine. The aqueous layer was washed severaltimes with ethyl acetate, and the organics were combined andconcentrated. The product was purified by flash chromatography (silicagel, ethyl acetate/hexanes gradient) and sonicated in a 15% ethylacetate in hexanes solution to provide 2.24 g (28%) of the product as anorange solid.

c. Preparation of compound 4(c)(2-(4-bromo-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acid ethylester). Compound 4(b) (10.59 g, 29.32 mmol) and acetonitrile (100 mL)were added to an oven-dried flask containing dry potassium carbonate(10.13 g, 73.30 mmol). The mixture was refluxed for one hour then cooledto room temperature. 2-Iodopropane (8.78 mL, 87.96 mmol) was added, andthe reaction mixture was heated to reflux temperature for 16 hours. Thereaction mixture was cooled to room temperature, concentrated, dissolvedin ethyl acetate, and filtered. The filtrate was concentrated in vacuo,and the crude product was recrystallized (ethyl acetate and hexanes) toprovide 9.38 g (79%) of the desired product as a tan solid.

d. Preparation of compound 4(d)(2-(4-bromo-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acid).Potassium hydroxide pellets (1.0 g, 17.82 mmol) were added to asuspension of compound 4(c) (2.02 g, 5.01 mmol) in 1:1 ethanol/water (25mL/25 mL). The reaction was heated to reflux for 2 hours. The reactionmixture was cooled to room temperature and concentrated in vacuo. Theproduct was extracted into ethyl acetate without acidification. Theorganic layer was concentrated, and the solid was recrystallized (ethylacetate and hexanes) to provide 1.86 g (99%) of the desired product asan orange solid.

e. Preparation of compound 4(e)(2-(4-bromo-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acidmethylamide). 1-(3-Dimethylaminopropyl)-3-ethylcarbodimide hydrochloride(1.40 g, 7.32 mmol), 1-hydroxybenzotriazole (0.99 g, 7.32 mmol) andmethylamine (4.88 mL, 2.0M in THF, 9.75 mmol) were added to a solutionof compound 4(d) (1.83 g, 4.88 mmol) in dichloromethane (35 mL). Thereaction mixture was stirred for 16 hours at room temperature, thenconcentrated, dissolved in ethyl acetate, and washed with water. Theorganic layer was concentrated in vacuo, and the crude product waspurified by flash chromatography (silica gel, ethyl acetate/hexanesgradient) to provide 1.24 g (66%) of the desired product as a yellowsolid.

f. Preparation of compound 4(f)(2-(4-cyano-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acidmethylamide). Copper cyanide (1.95 g, 21.81 mmol) was added to asolution of compound 4(e) (1.21 g, 3.12 mmol) in1-methyl-2-pyrrolidinone (NMP) (30 mL). The reaction mixture was heatedto 170° C. in an oil bath. The reaction was cooled to room temperature,diluted with water and ethyl acetate, and filtered through a Celite™plug, rinsing with ethyl acetate and water. The layers were separated,and the organic layer was concentrated in vacuo. The crude product waspurified by flash chromatography (silica gel, ethyl acetate/hexanesgradient) to provide 0.68 g (65%) of the desired product.

g. Preparation of compound 4(g)(2-(4-aminomethyl-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acidmethylamide, HCl salt). 10% Palladium on carbon (0.10 g) was mixed withwater and concentrated hydrochloric acid (0.5 mL) and added to areaction flask containing a solution of compound 4(f) (0.68 g, 2.03mmol) in methanol (15 mL). The reaction flask was shaken under 55 psigof hydrogen gas on a Parr shaker for 16 hours. The reaction mixture wasfiltered through Celite™, rinsing with ethanol. The filtrate wasconcentrated in vacuo, and the crude product was recrystallized (ethylacetate) to provide 0.65 g (86%) of the desired product as a dark yellowsolid.

h. Preparation of2-[4-(acetylamino-methyl)-phenyl]-5-isopropoxy-benzofuran-3-carboxylicacid methylamide. Triethylamine (0.037 mL, 0.267 mmol) was added to asuspension of compound 4(g) (50 mg, 0.133 mmol) in dichloromethane (10mL). Acetic anhydride (0.015 mL, 0.160 mmol) was added to the solution,and the reaction was stirred at room temperature. After 16 hours,dichloromethane (10 mL) and water (15 mL) were added to the mixture, andthe layers were separated. The organics were concentrated in vacuo, andthe crude product was purified by flash chromatography (silica gel,ethanol/ethyl acetate gradient) to provide 50 mg (96%) of the desiredproduct as an off-white solid.

Example 5 Preparation of2-(4-hydroxy-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acidmethylamide

a. Preparation of compound 5(a) (3-(4-benzyloxy-phenyl)-3-oxo-propionicacid ethyl ester). A mixture of ethyl malonate potassium salt (9.92 g,58.27 mmol) and magnesium chloride (4.17 g, 43.81 mmol) was refluxed inTHF (100 mL) under argon for 4 hours. In a second reaction vessel,1,1′-carbonyldiimidazole (CDI) (8.38 g, 51.70 mmol) was added to asolution of 4-benzyloxybenzoic acid (10 g, 43.81 mmol) in THF (60 mL)under argon. The solution was gently refluxed for 30 minutes. Bothreactions were cooled to room temperature, and the second solution wasadded dropwise to the ethyl malonate/magnesium chloride mixture. Thereaction was stirred at room temperature overnight. After 16 hours, ahydrochloric acid solution (20 mL concentrated HCl and 40 mL water) wasadded to the reaction mixture. The organic solvents were removed invacuo, and the crude product was extracted with ethyl acetate severaltimes. The organics were combined, washed with brine and concentrated.The product was purified by flash chromatography (silica gel, ethylacetate/hexanes gradient) to provide 10 g (77%) of the desired productas a pale yellow solid.

b. Preparation of compound 5(b)(2-(4-benzyloxy-phenyl)-5-hydroxy-benzofuran-3-carboxylic acid ethylester). Compound 5(a) (10.0 g, 33.52 mmol) was dissolved in ethanol (15mL) and added to an oven-dried flask containing zinc chloride(oven-dried, 4.57 g, 33.52 mmol). 1,4-Benzoquinone (3.62 g, 33.52 mmol)was placed in an addition funnel (wrapped with glass wool and aluminumfoil and using a cotton plug). The reaction mixture was heated to 100°C. in an oil bath, while regulating the amount of ethanol condensinginto the addition funnel to facilitate an 18-hour addition of the1,4-benzoquinone. When the 1,4-benzoquinone was consumed, the mixturewas cooled to room temperature, ethyl acetate was added, and the crudeproduct was washed with brine. The aqueous layer was washed severaltimes with ethyl acetate, and the organics were combined andconcentrated in vacuo. The product was purified by flash chromatography(silica gel, ethyl acetate/hexanes gradient) and sonicated in a 15%ethyl acetate in hexanes solution to provide 4.08 g (31%) of the desiredproduct as a solid.

c. Preparation of compound 5(c)(2-(4-benzyloxy-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acid ethylester). Compound 5(b) (4.07 g, 10.48 mmol) and acetonitrile (60 mL) wereadded to an oven-dried flask containing potassium carbonate (oven-dried,3.62 g, 26.20 mmol). The mixture was refluxed for one hour, and thencooled to room temperature. 2-Iodopropane (3.14 mL, 31.43 mmol) wasadded, and the mixture was again heated to reflux temperature. After 16hours, the reaction mixture was cooled to room temperature,concentrated, dissolved in ethyl acetate, and washed with water. Theorganics were concentrated in vacuo and purified by flash chromatography(silica gel, ethyl acetate/hexanes gradient) to provide 4.07 g (90%) ofthe product as a yellow solid.

d. Preparation of compound 5(d)(2-(4-benzyloxy-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acid).Potassium hydroxide pellets (0.5 g, 8.91 mmol) were added to asuspension of compound 5(c) (1.00 g, 2.32 mmol) in 1:1 ethanol/water (20mL/20 mL). The reaction mixture was heated to reflux for 2 hours, andthen cooled to room temperature. 1M Hydrochloric acid was added, and theprecipitate was filtered and dried to provide 0.92 g (99%) of theproduct as a white solid.

e. Preparation of compound 5(e)(2-(4-benzyloxy-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acidmethylamide). Compound 5(d) (0.92 g, 2.48 mmol) andbenzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate(1.29 g, 2.48 mmol) were combined under argon and treated withmethylamine (20 mL, 2.0M in THF). The solution was stirred at roomtemperature for 3 hours. The reaction mixture was concentrated,dissolved in ethyl acetate, and washed with water. The organics wereconcentrated and purified by flash chromatography (silica gel, ethylacetate/hexanes gradient) to provide 0.78 g (76%) of the desired productas a white solid.

f. Preparation of2-(4-hydroxy-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acidmethylamide. A mixture of 10% palladium on carbon (0.10 g) in water wasadded to mixture of compound 5(e) (0.78 g, 1.88 mmol) in anethanol/ethyl acetate (20 mL/10 mL) solution. The reaction mixture wasshaken under 55 psig of hydrogen gas on a Parr shaker for 6 hours. Thereaction mixture was filtered through Celite™, rinsing with ethylacetate and ethanol. The filtrate was concentrated, and the crudeproduct was recrystallized (ethyl acetate and hexanes) to provide 0.57 g(93%) of the desired product as an off white solid.

Example 6 Preparation of2-(4-fluoro-phenyl)-5-isopropoxy-6-pyrrolidin-1-yl-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 6(a) (3-(4-fluoro-phenyl)-3-oxo-propionicacid ethyl ester). 4-Fluorobenzoic acid (275 g, 1.96 mol) in THF (1 L)was added to a solution of 1,1′-carbonyldiimidazole (CDI) (381 g, 2.36mol) in THF (1 L) over a one hour period. The reaction mixture wasstirred at 30° C. for one hour, then at room temperature overnight.Magnesium chloride (186 g, 1.96 mol) was added over 5 minutes to asecond mixture of ethyl malonate potassium salt (435 g, 2.56 mol) in THF(2 L). The resulting mixture was stirred overnight in a closedapparatus. The first mixture was added to the malonate mixture over 1½hours. The reaction mixture was stirred for several hours at ambienttemperature, than warmed to 30° C. for several hours. The reactionmixture was treated with 4N HCl (1.0 L), and the layers were separated.The aqueous layer was diluted with water (1 L), acidified with HCl (250mL) until about pH 1, and washed with ethyl acetate (1 L). The ethylacetate layer was concentrated to provide 65 g of the crude product. Theoriginal organic layer was concentrated to remove the THF, diluted withethyl acetate (1 L), and rinsed with water (1 L). The organic layer wascombined with the 65 g of crude product and concentrated to an oil. Theoil was diluted with ethyl acetate (1 L) and rinsed with 5% aqueousNaHCO₃ (1 L). The organic layer was concentrated, and the crude productwas vacuum distilled to provide 322 g (78%) of the desired product.

b. Preparation of compound 6(b)(2-(4-fluoro-phenyl)-5-hydroxy-benzofuran-3-carboxylic acid ethylester). Compound 6(a) (157 g, 0.75 mol) was added to a flask containingzinc chloride (100 g, 0.74 mol) and ethanol (250 mL), and washed in withadditional ethanol (about 50 mL). 1,4-Benzoquinone (80 g, 0.74 mol) wasmixed with Celite™ (40 g) and placed in an addition funnel, which wasplugged lightly with glass wool. The reaction mixture was heated to 95°C., and the 1,4-benzoquinone was added at a rate of about 4 mL/min.After the 1,4-benzoquinone was consumed, the mixture was cooled to roomtemperature, ethyl acetate was added (2 L), and the crude product waswashed with water (1 L) and brine. Insoluble impurities were removed byfiltration, and the filtrate was concentrated. The resulting solid wasstirred in dichloromethane (500 mL) and cooled to −20° C. Additionalimpurities were removed by filtration. The filtrate was concentrated,and the crude product was mixed with dichloromethane (400 mL), cooled to−20° C., and filtered. The isolated solid was rinsed withdichloromethane and air-dried to provide 71.8 g (32.3%) of the desiredproduct.

c. Preparation of compound 6(c)(2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acid ethylester). Cesium carbonate (111.6 g, 343 mmol) was added to compound 6(b)(73.5 g, 245 mmol) in 1-methyl-2-pyrrolidinone (250 mL). The reactionmixture was heated to 50° C. in an oil bath for 16 hours, and thencooled to room temperature. The solid impurities were removed byfiltration, and the filtrate was diluted with brine and t-butylmethylether. The layers were separated, and the aqueous layer was rinsedseveral times with t-butylmethyl ether. The organic layers were combinedand concentrated. The solid, which formed overnight, was isolated byfiltration and rinsed with hexane to provide about 28 g of desiredproduct. The filtrate was purified by column chromatography (silica gel,ethyl acetate/hexanes gradient) to provide an additional 47.2 g ofdesired product.

d. Preparation of compound 6(d)(6-bromo-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acidethyl ester). A solution of bromine (0.75 mL, 0.014 mol) in anhydrousdioxane (20 mL) was added dropwise over 1 hour to a solution of compound6(c), which can be prepared according to the previous step (4.59 g,0.014 mol) in anhydrous dioxane (50 mL). The reaction mixture wasstirred for 1 hour under argon, at room temperature under a 300-wattlamp. An additional 3 drops of bromine were added, and the reaction wasallowed to stir overnight. The reaction mixture was concentrated to ½volume, diluted with water, extracted with ethyl acetate, dried withMgSO₄, and concentrated. The crude product was purified by HPLC (reversephase, acetonitrile/water gradient) to provide the desired product as awhite solid.

e. Preparation of compound 6(e)(2-(4-fluoro-phenyl)-5-isopropoxy-6-pyrrolidin-1-yl-benzofuran-3-carboxylicacid ethyl ester). An oven-dried flask containing cesium carbonate(dried, 0.271 g) was placed in a dry bag under argon, and compound 6(d)(0.250 g, 0.594 mmol), tris(dibenzylideneacetone)-dipalladium(0) (0.0163g, 0.0178 mmol) and rac-2,2-bis(diphenylphosphino)-1,1′-binaphthyl(racemic mixture, 0.011 g, 0.0177 mmol) were added. The flask wasremoved from the dry bag, purged, and evacuated with argon (3×).Anhydrous toluene (1.0 mL), followed by pyrrolidine (0.059 mL) wereadded to the flask. The reaction mixture was heated to 95° C. in an oilbath overnight, and then cooled to room temperature, diluted withdiethyl ether, filtered through a pad of Celite™, and washed withdiethyl ether. The solvents were evaporated, and the crude product waspurified by flash chromatography (silica gel, ethyl acetate/hexanes) toprovide 0.117 g (49%) of the desired product as a yellow oil.

f. Preparation of compound 6(f)(2-(4-fluoro-phenyl)-5-isopropoxy-6-pyrrolidin-1-yl-benzofuran-3-carboxylicacid). Potassium hydroxide was added (1 pellet) to a solution ofcompound 6(e) (0.114 g, 0.277 mmol) in 2:1 ethanol/water (2.0 mL/1.0mL). The reaction mixture was heated to reflux over a 2-hour period, andthen stirred at room temperature overnight. Ethanol was removed from themixture by evaporation. The remaining oil was dissolved in water andacidified with 3N hydrochloric acid until a solid formed (around pH7.5). The yellow solid was filtered to provide 0.09 g (85%) of thedesired product.

g. Preparation of 2-(4-fluoro-phenyl)-5isopropoxy-6-pyrrolidin-1-yl-benzofuran-3-carboxylic acid methylamide.Benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate(0.107 g, 0.183 mmol) was added to a solution of compound 6(f)SBE-0628-198 (79.0 mg, 0.206 mmol) in methylamine (3.0 mL, 2.0M in THF)in an oven-dried flask under an argon atmosphere. The reaction mixturewas allowed to stir at room temperature for 6 hours, then concentratedin vacuo. The resulting oil was purified by flash chromatography (silicagel, ethyl acetate/hexanes) to provide 0.045 g (63%) of the product as ayellow solid.

Example 7 Preparation of5-difluoromethoxy-2-(4-fluoro-phenyl)-benzofuran-3-carboxylic acidmethylamide

a. Preparation of compound 7(a)(5-difluoromethoxy-2-(4-fluoro-phenyl)-benzofuran-3-carboxylic acidethyl ester). Potassium iodide (28 mg, 0.167 mmol) and potassiumcarbonate (0.69 g, 5.00 mmol) were added to a solution of compound 6(b),which can be prepared according to Example 6 (0.50 g, 1.67 mmol) in2-butanone (20 mL). The reaction mixture was stirred for 10 minutes atroom temperature. Ethyl chlorodifluoroacetate (0.32 mL, 2.50 mmol) wasadded, and the reaction was refluxed for 16 hours. The reaction wascooled to room temperature and concentrated in vacuo. The crude productwas dissolved in ethyl acetate and washed with water and 1M hydrochloricacid. The product was concentrated and purified by flash chromatography(silica gel, ethyl acetate/hexanes gradient) to provide 130 mg (22%) ofthe desired product as a white solid.

b. Preparation of compound 7(b)(5-difluoromethoxy-2-(4-fluoro-phenyl)-benzofuran-3-carboxylic acid).Potassium hydroxide pellets (0.50 g, 8.91 mmol) were added to asuspension of compound 7(a) (0.13 g, 0.371 mmol) in 1:1 ethanol/water (7mL/7 mL). The reaction mixture was heated to reflux for 1.5 hours. Thereaction mixture was cooled to room temperature and concentrated invacuo. 1M Hydrochloric acid was added until the solution became acidic,forming a precipitate. The solid was filtered and dried to provide 120mg (100%) of the desired product as a white solid.

c. Preparation of5-difluoromethoxy-2-(4-fluoro-phenyl)-benzofuran-3-carboxylic acidmethylamide. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(0.11 g, 0.558 mmol), 1-hydroxybenzotriazole (75 mg, 0.558 mmol) andmethylamine (2.0M in THF, 0.37 mL, 0.745 mmol) were added to a solutionof compound 7(b) (0.12 g, 0.372 mmol) in dichloromethane (10 mL). Thereaction mixture was stirred for 16 hours at room temperature, thenconcentrated, dissolved in ethyl acetate and washed with water. Theorganic layer was concentrated, and the crude product was purified byflash chromatography (silica gel, ethyl acetate/hexanes gradient) toprovide 87 mg (70%) of the desired product as a white solid.

Example 8 Preparation of2-(4-fluoro-phenyl)-5-isopropoxy-6-(2-methoxy-ethylamino)-benzofuran-3-carboxylicacid methylamide

The title compound (0.038 g, yellow solid) was prepared essentiallyaccording to the general procedure described in Example 6 above;however, in step e no dry bag was used and 2-methoxyethylamine was usedinstead of pyrrolidine. Also, the title compound was purified by reversephase HPLC using a gradient of 60% to 90% acetonitrile in water.

Example 9 Preparation of 5-methyl-2-phenyl-benzofuran-3-carboxylic acidmethylamide

a. Preparation of compound 9(a) (3-methoxy-6-methyl-2-phenylflavyliumchloride). Dry HCl gas was bubbled through a solution of2-hydroxy-5-methylbenzaldehyde (2.0 g, 14.69 mmol) and2-methoxyacetophenone (2 mL, 14.51 mmol) in ethyl acetate (28 mL) andethanol (7 mL) at 0° C. for one hour. The reaction was then capped andplaced in the refrigerator for 56 hours. Diethyl ether was added until aprecipitate formed. The solid was isolated by filtration to provide 3.73g (88%) of the desired salt.

b. Preparation of compound 9(b)(5-methyl-2-phenyl-benzofuran-3-carboxylic acid methyl ester). Hydrogenperoxide (7.5 mL, 72.8 mmol) was added to a suspension of compound 9(a)(3.5 g, 12.20 mmol) in 50% aqueous methanol (72 mL). The reaction washeated to reflux temperature overnight, cooled to room temperature anddiluted with ether. The layers were separated, and the aqueous phase wasextracted with diethyl ether (2×). The organics were combined, washedwith brine, dried (MgSO₄) and evaporated. Purification by columnchromatography on silica gel using 5:1 hexane/ethyl acetate as eluantafforded 736 mg (22.6%) of the desired compound as a yellow solid.

c. Preparation of compound 9(c)(5-methyl-2-phenyl-benzofuran-3-carboxylic acid). Aqueous potassiumhydroxide (4N, 12 mL) was added to a suspension of compound 9(b) (655mg, 2.46 mmol) in methanol (15 mL). The reaction was stirred at anelevated temperature overnight. The mixture was cooled to roomtemperature and acidified with 1N hydrochloric acid to pH 2. Theprecipitate was collected by suction filtration, washed with water anddried to give 471 mg (76%) of the desired carboxylic acid.

d. Preparation of 5-methyl-2-phenyl-benzofuran-3-carboxylic acidmethylamide. To a solution of compound 9(c) (125 mg, 0.495 mmol) in drydichloromethane (2 mL) was added methylamine (0.495 mL of 2M solution inTHF, 0.99 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimidehydrochloride (142 mg, 0.742 mmol) and hydroxybenzotriazole (100 mg,0.742 mmol), respectively. The reaction was stirred at room temperatureunder argon overnight, quenched with 1N hydrochloric acid and extractedwith dichloromethane. The organic layer was washed with brine, dried(MgSO₄) and evaporated. Purification by column chromatography on silicagel using dichloromethane as eluant afforded 49 mg (37%) of the titleproduct as a white solid.

Example 10 Preparation of5-methyl-2-(4-fluoro-phenyl)-benzofuran-3-carboxylic acid methylamide

a. Preparation of compound 10(a)(1-(4-fluoro-phenyl)-2-methoxy-ethanone). A solution of 4-fluorobenzoylchloride (25.6 g, 161 mmol) in acetonitrile (60 mL) was added dropwiseto a solution of trimethylsilyl diazomethane (96 mL of 2M solution,193.2 mmol) and triethylamine (27 mL, 193.2 mmol) in anhydrousacetonitrile (250 mL) at 0° C. under an argon atmosphere. The reactionwas stirred for two hours at 0° C. and then capped and placed in therefrigerator overnight. The solvent was removed via rotary evaporation,and the residue was taken up in saturated sodium bicarbonate solutionand extracted with ethyl acetate. The organics were washed with waterand brine, dried (MgSO₄) and evaporated to give 25.16 g of a yellowsolid. The solid was dissolved in anhydrous methanol (200 mL), and borontrifluoride diethyl etherate (19.4 mL, 161 mmol) was added. The reactionwas stirred at room temperature for 2 hours, and the solvent was removedvia rotary evaporation. The residue was dissolved in diethyl ether andwashed with water and brine, dried (MgSO₄) and evaporated. Purificationby column chromatography on silica gel using 5:1 hexanes/ethyl acetateafforded 18.77 g (69%) of the desired product as an orange solid.

b. Preparation of 5-methyl-2-(4-fluoro-phenyl)-benzofuran-3-carboxylicacid methylamide. The title compound was prepared essentially accordingto Example 9, steps a-b; however in step a2-methoxy-4′-fluoroacetophenone was used instead of2-methoxyacetophenone and compound 10(a) was used instead of2-methoxyacetophenone.

Example 11 Preparation of2-phenyl-5-(2,2,2-trifluoro-ethoxy)-benzofuran-3-carboxylic acid methylamide

a. Preparation of compound 11(a)(5-hydroxy-2-phenyl-benzofuran-3-carboxylic acid). Compound 11(a) wasprepared essentially according to the general procedure described inExample 3, step d above; however, compound 2(a) was used instead ofcompound 3(c).

b. Preparation of Resin 11(b).

4-Formyl-3-methoxyphenoxymethyl functionalized styrene/divinylbenzenecopolymer (2 g; Aldrich, 0.9 mmol/g) was swelled in 1% acetic acid indichloroethane (20 mL) and then drained. Addition of 1% acetic acid indichloroethane (20 mL) was followed by methylamine (2M in THF, 4 mL),and the mixture was sonicated for 20 minutes. The resin mixture was thenallowed to stand at room temperature for 16 hours. A sonicatedsuspension of sodium acetoxy borohydride (422 mg, 2 mmol) in 1% aceticacid in dichloroethane (5 mL) was then added followed by mild agitationat room temperature for 16 hours. Methanol (5 mL) was added, and thesolvents were drained. The resin was then extensively washed in methanoland dichloromethane. The reaction was repeated to ensure completeconsumption of the resin bound aldehyde. The dried resin was taken on tothe next step without characterization.

c. Preparation of Resin 11(c).

The resin 11(b) was swelled in DMF (6 mL) and then compound 11(a) (325mg, 1.5 mmol) was added followed by the addition ofbenzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate(780 mg, 1.5 mmol; NovaBiochem), diisopropyl ethylamine (0.523 mL, 3mmol), and DMF (4 mL). The reaction mixture was gently agitated undernitrogen for 4 hours and then drained. The resin was washed extensivelywith DMF (6×10 mL), methanol (6×10 mL) and dichloromethane (6×10 mL) anddried under vacuo. The dried resin was continued to step d.

A small sample was subjected to treatment with 25% trifluoroacetic acid(TFA) in dichloromethane (CH₂Cl₂) for a qualitative assessment of resinloading. After 30 min, the TFA-CH₂Cl₂ mixture was filtered, and thefiltrate was evaporated to dryness. Characterization by LC-MS and NMR ofdried product from TFA treatment revealed that the resin loading wassuccessful.

d. Preparation of2-phenyl-5-(2,2,2-trifluoro-ethoxy)-benzofuran-3-carboxylic acidmethylamide. Cesium carbonate (325 mg, 1 mmol) was mixed with DMF (2 mL)and heated to 75° C. for 15 minutes. The resin 11(c) (150 mg, about0.135 mmol) was added as a solid followed by 2,2,2-trifluoroethyl iodide(210 mg, 1 mmol) and DMF (2 mL). The reaction mixture was heated undernitrogen at 75° C. for 18 hours. The resin was then cooled to roomtemperature and washed extensively with DMF (6×0 mL), methanol (6×10 mL)and dichloromethane (CH₂Cl₂) (6×10 mL) and dried under vacuo. The driedresin was treated with 25% TFA in CH₂Cl₂ for 60 minutes. The TFA-CH₂Cl₂mixture was filtered, and the filtrate was evaporated to dryness. Thedried crude product was then purified by reverse phase HPLC on a GilsonHPLC-MS semi-prep system (eluting with 0.1% acetic acid inacetonitrile/water) to provide 12.7 mg (27%) of the desired product.

Example 12 Preparation of2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acid methylamide

a. Preparation of compound 12(a)(i) and compound 12(a)(ii)(2-(4-fluoro-phenyl)-5-hydroxy-benzofuran-3-carboxylic acid methyl esterand 2-(4-fluoro-phenyl)-5-hydroxy-benzofuran-3-carboxylic acid ethylester). In an oven-dried flask under argon was placed methyl4-fluorobenzoylacetate (4.0 g, 20.4 mmol), zinc chloride (anhydrous,2.73 g, 20.4 mmol) and absolute ethanol (8 mL) with magnetic stirring.Solid 1,4-benzoquinone (2.21 g, 20.4 mmol) was placed in an additionfunnel atop the reaction flask. The reaction was heated in an oil bathuntil gently refluxing, with the hot ethanol slowly dissolving anddripping the 1,4-benzoquinone into the pot over a period of 18 hours.The reaction was cooled to room temperature and diluted with ethylacetate (40 mL) and water. After extraction with ethyl acetate (2×), theorganics were combined, dried with Na₂SO₄, filtered through silica gel,and evaporated. The resulting residue was filtered then purified by HPLC(silica gel, 40% ethyl acetate in hexanes), and the crude product wasfurther purified via crystallization from hot ethyl acetate/hexanes toprovide 2.09 g (36%) of a mixture of compound 12(a)(i) and compound12(a)(ii).

b. Preparation of compound 12(b)(i) and compound 12(b)(ii)(2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acid methyl esterand 2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acid ethylester). Methyl iodide (0.43 mL, 6.99 mmol) was added to a mixture of thecompounds 12(a)(i) and 12(a)(ii) (1.00 g, 3.49 mmol), potassiumcarbonate (milled, 1.21 g, 8.73 mmol) and anhydrous acetonitrile (15 mL)under an argon atmosphere. The reaction mixture was heated to refluxunder argon for 18 hours, and then cooled to room temperature andstirred for 24 hours. The mixture was diluted with acetonitrile (10 mL)and filtered, followed by evaporation of the solvent. The crude solidwas diluted with 60:40 ethyl acetate/hexanes, re-filtered, and purifiedby HPLC (silica gel, ethyl acetate/hexanes) to provide 0.85 g (78%) ofthe desired product.

c. Preparation of compound 12(c)(2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acid). Compoundmixture 12(b) (0.85 g, 2.70 mmol) was combined with potassium hydroxidepellets (0.23 g, 4.06 mmol) in ethanol (24 mL) and water (4 mL). Themixture was gently refluxed overnight and cooled to room temperature.The solvent was removed by rotary evaporation, and the remaining solidwas dissolved in water. Acidification with 3M HCl precipitated a solidthat was filtered, washed with water and hexanes, and partially driedunder vacuum to provide 0.84 g of the desired product.

d. Preparation of compound 12(d)(2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acidmethylamide). 1,1′-Carbonyldiimidazole (42 mg, 0.262 mmol) was added toa solution of compound 12 (c) (50 mg, 0.175 mmol) in anhydrous THF (3mL) under argon. The reaction mixture was gently heated for 30 minutesto drive off CO₂, after which ethylamine in excess (40% by weight inwater, 1 mL) was added. The reaction mixture was stirred at roomtemperature overnight. The solvent was evaporated, and the crude productwas purified by HPLC (reverse-phase C18, 1 mL dimethyl sulfoxide inacetonitrile/water, 2×). The acetonitrile was removed by rotaryevaporation, and a solid was isolated by filtration and washed withwater and hexanes to provide 14.3 mg (28%) of the desired product.

Example 13 Preparation of6-bromo-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acidmethylamide

a. Preparation of compound 13(a)(6-bromo-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acidethyl ester). A solution of bromine (127 mg, 0.795 mmol) in anhydrousdioxane (1 mL) was added dropwise over 20 minutes to a solution ofcompound 12(b)(ii), prepared essentially according to Example 12, step b(250 mg, 0.795 mmol) in anhydrous dioxane (3 mL). The reaction wasstirred at room temperature, under a 300-watt lamp, for 3 hours underargon. The reaction mixture was diluted with water, and the solids werefiltered, washed with water and hexanes, and dried in a vacuum oven. Thecrude product was purified by HPLC (reverse phase, acetonitrile/watergradient) to provide 47 mg (15%) of the desired product as a whitesolid.

b. Preparation of6-bromo-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acidmethylamide. The title compound was prepared essentially according tothe general procedure described in Example 1, steps c and d, above;however compound 13(a) was used in step c instead of compound 1(b).

Example 14 Preparation of5-methoxy-6-methyl-2-phenyl-benzofuran-3-carboxylic acid methylamide

a. Preparation of compound 14(a)(i) and compound 14(a)(ii)(5-hydroxy-6-methyl-2-phenyl-benzofuran-3-carboxylic acid ethyl esterand 5-hydroxy-7-methyl-2-phenyl-benzofuran-3-carboxylic acid ethylester). Absolute ethanol (30 mL) and ethyl benzoylacetate (9.9 mL, 57.3mmol) were added to an oven-dried flask containing anhydrous ZnCl₂ (7.8g, 57.3 mmol, pre-dried in oven for 1 hour) under argon.Methyl-1,4-benzoquinone (7.0 g, 57.3 mmol) was placed in an additionfunnel with a side arm (a pad of glass wool at the bottom of funnel),and a condenser was equipped on the top of the addition funnel. Thereaction mixture in the flask was slowly heated in oil bath. Ethanolrefluxed through the side arm of the addition funnel (wrapped with glasswool and aluminum foil), and then slowly washed down themethyl-1,4-benzoquinone overnight (18 hours). The reaction mixture wascooled to room temperature, diluted with ethyl acetate (about 200 mL),washed with water (2×300 mL), and dried over Na₂SO₄. Afterconcentration, the residue was purified by column chromatography (dryloading onto silica gel, ethyl acetate/hexane solvent gradient) andcrystallized from hot ethyl acetate/hexanes in two crops, yielding amixture of compound 14(a)(i) and compound 14(a)(ii), which was carriedforward to the next step without further purification.

b. Preparation of compound 14(b)(i) and compound 14(b)(ii)(5-methoxy-6-methyl-2-phenyl-benzofuran-3-carboxylic acid ethyl esterand 5-methoxy-7-methyl-2-phenyl-benzofuran-3-carboxylic acid ethylester). In an oven-dried 50 mL flask under argon was combined compoundmixture 14(a) (1.00 g, 3.37 mmol), potassium carbonate (milled, 1.16 g,8.42 mmol) and anhydrous acetonitrile (20 mL). Methyl iodide (0.42 mL,6.75 mmol) was added to this mixture, and the reaction was heated toreflux under argon for 3 hours. The reaction mixture was cooled to roomtemperature, and the solvent was removed by rotary evaporation. Theresidue was diluted with ethyl acetate and filtered, followed byevaporation of the solvent. The resulting oil was diluted with hexanes,and a solid was isolated by filtration. The crude product was purifiedby HPLC (silica gel, ethyl acetate/hexanes) to provide 0.135 g ofcompound 14(b)(i) and 0.432 g of compound 14(b)(ii).

c. Preparation of 5-methoxy-6-methyl-2-phenyl-benzofuran-3-carboxylicacid methylamide. The title compound was prepared essentially accordingto the general procedure described in Example 12, steps c and d above;however, compound 14(b)(i) was used in step c instead of compound 12(b).

Example 15 Preparation of6-(3-amino-pyrrolidin-1-yl)-2-(4-fluoro-phenyl)-5-isopropoxy-2,3-dihydro-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 15(a)(6-(3-tert-butoxycarbonylamino-pyrrolidin-1-yl)-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylicacid ethyl ester). Anhydrous cesium carbonate (270 mg, 0.830 mmol),bis(dibenzylideneacetone)-dipalladium(0) (11 mg, 0.0119 mmol),rac-2,2-bis(diphenylphosphino)-1,1-binaphthyl (11 mg, 0.0178 mmol),3-(tert)-butoxycarbonylamino)pyrrolidine (0.132 g, 0.712 mmol) andcompound 6(d), which can be prepared according to Example 6 (250 mg,0.593 mmol) were placed in an oven dried 2-neck flask, which wasdegassed and purged several times with argon. Anhydrous toluene (2 mL)was syringed into the reaction mixture, and the reaction flask waspurged with argon. The reaction was stirred under argon for 18 hours at80° C., then cooled to room temperature, diluted with diethyl ether (8mL), and filtered through a pad of silica gel. The solvent wasevaporated, and the resulting oil was purified by HPLC (reverse phase,acetonitrile/water gradient) to provide the desired product.

b. Preparation of compound 15(b)(6-(3-amino-pyrrolidin-1-yl)-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylicacid). Compound 15(a) was combined with three potassium hydroxidepellets (approximately 0.4 g) in ethanol (30 mL) and water. The mixturewas gently refluxed overnight and cooled to room temperature. Themixture was acidified with 6M acetic acid to about pH 6 and treated withsaturated aqueous sodium bicarbonate until a precipitate formed. Thesolid was filtered, rinsed with water and hexanes, and dried in vacuo,to provide 86 mg of the desired product.

c. Preparation of6-(3-amino-pyrrolidin-1-yl)-2-(4-fluoro-phenyl)-5-isopropoxy-2,3-dihydro-benzofuran-3-carboxylicacid methylamide. Benzotriazol-1-yloxytrispyrrolidinophosphoniumhexafluorophosphate (PyBOP) (123 mg, 0.216 mmol) was added to a mixtureof methylamine (10 mL, 2.0M in THF) and compound 15(b) (86 mg, 0.216mmol) in anhydrous DMF (5 mL) under argon. The resulting reactionmixture was stirred at room temperature for 30 minutes, and concentratedon a rotary evaporator. The crude solid was sonicated and dissolved inethyl acetate. The solution was washed with water, dried, andconcentrated. The crude product was purified by prep HPLC (reverse phaseC18, acetonitrile/water, with 4 drops of dimethyl sulfoxide tosolubilize the product) to provide 20 mg of the title product.

Example 16 Preparation of6-amino-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acidmethylamide

a. Preparation of compound 16(a)(2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acid).Compound 6(c), which can be prepared according to Example 6 (18.5 g, 5.4mmol) was added to a stirred solution of potassium hydroxide (9.1 g,0.612 mol) in 1:1 ethanol/water (200 mL). After stirring for 12 hours atreflux temperature, the solvent was removed, and the remaining slurrywas dissolved in water and extracted with t-butylmethylether. Theorganic layer was discarded, and the aqueous was acidified with 3N HCl.A solid was isolated by filtration, rinsed with water and hexanes, anddried in a vacuum oven at 60° C. to provide 15.0 g (88%) of the desiredproduct.

b. Preparation of compound 16(b)(2-(4-fluoro-phenyl)-5-isopropoxy-6-nitro-benzofuran-3-carboxylic acid).In a 500 mL 3-neck flask fitted with a thermometer, a mechanicalstirrer, and an addition funnel for solid, was poured a (4:1) mixture ofconcentrated (70%) nitric acid (200 mL) and glacial acetic acid (50 mL).The solution was cooled to −10° C. with an ethanol/dry ice bath.Compound 16(a), which can be prepared according to the preceding step,(10.0 g, 31.8 mmol) was added portionwise over a 15-minute period. Thereaction was stirred at −10° C. for one hour, than allowed to warm up to10° C. for 4 additional hours. The suspension was poured carefully intoice-cold water, and the precipitate was collected by filtration, washedthoroughly with water, then air-dried. The yellow powder was a mixture16:84 of the 4- and 6-nitro isomers. The isomers were separated via arecrystallization (150 mL of ethyl acetate with 2 mL of hexanes addeddropwise until cloudy) to provide 8.2 g (72%) of the desired product asa yellow powder.

c. Preparation of compound 16(c)(2-(4-fluoro-phenyl)-5-isopropoxy-6-nitro-benzofuran-3-carboxylic acidmethylamide). 1-Hydroxybenzotriazole (purity 98%, 2.82 g, 20.9 mmol),followed by anhydrous dichloromethane (70 mL) were added to compound16(b) (5 g, 13.9 mmol) in a dry 100 mL flask under dry argon.1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4 g, 20.9mmol) and was then introduced. Finally, methylamine solution (2M in THF,13.9 mL, 27.8 mol) was added to the slurry, while stirring vigorously.The reaction mixture was stirred at room temperature overnight. Thereaction mixture was diluted with dichloromethane (120 mL), then washedwith water (3×) and brine (3×). The organic layer was separated, driedover magnesium sulfate, and filtered through a silica gel pad, rinsingwith ethyl acetate. Concentration of the organic layers afforded 5.01 g(97%) of the desired product.

d. Preparation of6-amino-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acidmethylamide.

To a sonicated suspension of compound 16(c), which can be preparedaccording to step c above, (2.0 g, 10.7 mmol) in ethyl acetate (125 mL)was added activated 10% palladium on carbon (200 mg, 10% weight). Themixture was allowed to stir under 50 psig of hydrogen gas on aParr-shaker overnight. The reaction was then filtered through a pad ofCelite™, rinsing with a 9:1 mixture of ethyl acetate/methanol.Concentration of the filtrate gave 1.78 g (97%) of pure expectedcompound.

Example 17 Preparation of6-amino-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acidmethylamide

a. Preparation of compound 17(a)(2-(4-fluoro-phenyl)-5-methoxy-6-nitro-benzofuran-3-carboxylic acid).The intermediate compound was prepared essentially according to thegeneral procedure described in Example 16, step b above; however,compound 12(c) was used instead of compound 16(a).

b. Preparation of compound 17(b)(2-(4-fluoro-phenyl)-5-methoxy-6-nitro-benzofuran-3-carboxylic acidmethylamide). To a suspension of compound 17(a) (2.0 g, 6.04 mmol) inanhydrous dichloromethane (50 mL) was added methylamine (6 mL, 2M inTHF), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride(EDCI) (1.74 g, 9.06 mmol) and hydroxybenzotriazole (1.22 g, 9.06 mmol),respectively. The mixture was allowed to stir overnight. The reactionwas quenched with water (100 mL) and diluted with dichloromethane (50mL). The layers were separated, and the aqueous phase was extracted withdichloromethane (3×). The combined organics were washed with water thenbrine, dried over MgSO₄, and concentrated. The oil was triturated underhexanes/ether (3:1) in order to afford a yellow solid, which wasfiltered and air-dried. This reaction yielded 2.0 g (97%) of theexpected compound.

c. Preparation of6-amino-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acidmethylamide. The title compound was prepared essentially according tothe general procedure described in Example 16, step d above; however,compound 17(b) was used instead of compound 16(c).

Example 18 Preparation of6-acetylamino-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acidmethylamide

Diisopropylethylamine (83.2 μL, 477 μmol), followed by acetic anhydride(239 μmol) were added to a solution of6-amino-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acidmethylamide, prepared according to Example 17 (75 mg, 239 μmol) in drytrichloromethane (3 mL). After one hour, the reaction was quenched withwater (3 mL). After concentration to dryness, the crude oil was purifiedby HPLC (reverse phase, C18, acetonitrile/water with 0.1% acetic acid)to provide 73 mg (87%) of the title compound.

Example 19 Preparation of2-(4-fluoro-phenyl)-5-isopropoxy-6-methylamino-benzofuran-3-carboxylicacid methylamide

6-Amino-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acidmethylamide, prepared according to Example 16 (55 mg, 161 μmol) wasdissolved in anhydrous diethyl ether (2 mL). Triethylamine (25 μL, 193μmol) was added to the reaction mixture, followed by the slow additionof dimethylsulfate (17 μL, 177 μmol). Water (1 mL) was added after 2hours. The reaction was concentrated to dryness, and the crude productwas purified on HPLC (reverse phase) to provide 32 mg (56%) of pureproduct.

Example 20 Preparation of6-dimethylamino-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylicacid methylamide

The title compound (35 mg, 59%) was prepared essentially according tothe general procedure in Example 19, however the equivalents oftriethylamine and dimethylsulfate were doubled.

Example 21 Preparation of2-(4-fluoro-phenyl)-5-isopropoxy-6-methanesulfonylamino-benzofuran-3-carboxylicacid methylamide

6-Amino-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acidmethylamide, prepared according to Example 16 (100 mg, 292 μmol) wasdissolved in dry dichloromethane (3 mL) under an argon atmosphere. Thereaction was cooled down to 0° C. with an ice bath. Pyridine (16.83 μL,321 μmol) and methanesulfonyl chloride (22.61 μL, 292 μmol) were mixedtogether under argon, and then added dropwise to the first anilinesolution. The reaction mixture was allowed to warm to room temperaturefor 1 hour. The reaction mixture was diluted with water (20 mL) andextracted with dichloromethane (3×10 mL). The combined organic layerswere washed with a 1N HCl solution, water, a saturated aqueousbicarbonate solution and brine and concentrated in vacuo. The crudeproduct was purified by column chromatography (silica gel, 20 to 50%ethyl acetate in hexanes gradient) to provide 68 mg (56%) of theproduct.

An Alternative Method for Preparing2-(4-fluoro-phenyl)-5-isopropoxy-6-methanesulfonylamino-benzofuran-3-carboxylicacid methylamide is as Follows:

a. Preparation of compound 21(a) (3-(4-fluoro-phenyl)-3-oxo-propionicacid ethyl ester). A slurry of ethyl malonate, potassium salt (1.58 kg,9.28 mol) in THF (8.0 L) was treated with magnesium chloride (0.68 kg,7.14 mol) in one portion. The exothermic reaction was stirred for 6hours at 65-70° C., then at ambient temperature overnight. Meanwhile, asolution of fluorobenzoic acid (1.00 kg, 7.14 mol) in THF (3.7 L) wasslowly added to a mixture of 1,1′-carbonyldiimidazole (1.39 kg, 8.56mol) in THF (3.7 L) and stirred at 30° C. for 2 hours. The solution wasadded to the ethyl malonate mixture over a 1¼-hour period at 20-30° C.and stirred overnight at 30° C.

The mixture was cooled to 20° C. and neutralized with dilute HCl (4N,7.0 L), and the aqueous layer was removed. The solution wasconcentrated, and the product was collected by hi-vac distillation. Theresulting solution was dissolved in ethyl acetate and rinsed with 5%sodium bicarbonate. The organic layer was concentrated, and the productwas collected by distillation to provide 1.36 kg of the desired productas a colorless oil.

Compound 21(a) Can Also be Prepared According to the FollowingProcedure:

Toluene (7.20 kg) was added to a flask containing potassium-t-butoxide(2.60 kg, 23.17 mol) under a nitrogen atmosphere. The mixture wasagitated, and then diethyl carbonate (6.61 kg, 55.96 mol) was added overa 20-minute period. The reaction was heated to >78° C. for over an hour.The reaction was cooled to about 70° C., and 4-fluoroacetophenone (2.00kg, 14.91 mol) was added over a 1-hour period, rinsing with toluene (0.3kg). The reaction was stirred for an additional hour at about 70-75° C.The reaction was cooled to room temperature, and stirred overnight. Asolution of hydrochloric acid and water (3.3 L concentrated HCL in 8.7kg water) was added, and the reaction was mixed for 10 minutes. Thelayers were separated, and the aqueous layer was rinsed with water (2.0L) and 5% sodium bicarbonate (0.1 kg). The product was isolated byvacuum distillation, to provide 2.44 kg (80%) of the desired product.

b. Preparation of compound 21(b)(2-(4-fluoro-phenyl)-5-hydroxy-benzofuran-3-carboxylic acid ethylester). A solution of p-benzoquinone (617 g, 5.71 mol) in THF (3.6 L)was added over 6 hours to a solution of anhydrous zinc chloride (778-810g, about 5.7 mol) and compound 21(a) (1200 g, 5.71 mol) in ethanol (2 L)at 105° C., distilling off THF to maintain this temperature. After onehour, the reaction was quenched in water/ethyl acetate (6 L/8 L). Theinsoluble materials were removed by filtration, and the organic layerwas washed with water (3 L) and concentrated to dryness. The solids wereslurried in dichloromethane (2 L) and filtered. The isolated solids weresuspended in ethanol (2 L), stirred, and cooled to <0° C. The solidswere collected by filtration to obtain 1012 g of the desired product asa white solid.

¹H NMR in CDCl₃ (300 MHz): 8.02 (m, 2H); 7.51 (d, 1H, J=2.90 Hz); 7.38(d, 1H); 7.16 (m, 2H); 6.88 (dd, 1H, J−8.70, 2.79); 5.09 (s, 1H); 4.40(q, 2H, J=7.2 Hz); 1.40 (t, 3H, J=7.20 Hz). Mass Spec: (M+1)=301.

c. Preparation of compound 21(c)(2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acid ethylester). A solution of compound 21(b) (2.35 kg, 7.83 mol) in1-methyl-2-pyrrolidinone (8.3 L) was treated with cesium carbonate (5.10kg. 15.65 mol) over a ten-minute period. 2-Bromopropane (2.98 kg, 24.26mol) was added, then the mixture was heated overnight at 50° C. Thereaction was added to dilute ammonium hydroxide (1.8 L) and agitated for30 minutes. The mixture was diluted with water (11.8 L) and extractedwith heptane (14.7 L). The layers were separated, and the organic layerwas rinsed with water. And concentrated by rotary evaporation to providean oil which solidified to give the product in quantitative yield.

¹H NMR in CDCl₃ (300 MHz) 8.02 (m, 2H); 7.56 (d, 1H, J=2.34 Hz); 7.40(d, 1H, J=8.79 Hz); 7.16 (t, 2H, J=8.79 Hz); 6.95 (dd, 1H, J−8.79 Hz),4.59 (m, 1H), 4.41 (q, 2H, J=7.03 Hz) and 1.39 (m, 9H). Mass Spec:(M+1)=343.

d. Preparation of compound 21(d)(2-(4-fluoro-phenyl)-5-isopropoxy-6-nitro-benzofuran-3-carboxylic acidethyl ester). A solution of compound 21(c) (2.68 kg, 7.83 mol) inchloroform was added slowly to a cooled mixture of chloroform (13.4 kg,ethanol can also be used) and 70% nitric acid (6.7 kg), at a temperatureof about 20° C. After one hour, the mixture was allowed to come to roomtemperature and diluted with water (8.6 L). The organic layer wasseparated, washed and concentrated to a solid. The crude product wasmixed with t-butylmethyl ether and agitated for one hour. The solid wascollected by filtration, rinsed with heptane, and dried to afford 2.43kg (80%) of desired product.

¹H NMR in CDCl₃ (300 MHz): 8.05 (m, 2H); 8.00 (s, 1H), 7.76 (s, 1H),7.20 (m, 2H), 4.71 (septuplet, 1H, J=6.00 Hz); 4.42 (q, 2H, J=7.20 Hz);1.45 (d, 6H, J=6.00 Hz); 1.41 (t, 3H, J=7.20 Hz). Mass Spec: (M+1)=388.

e. Preparation of compound 21(e)(6-amino-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acidethyl ester). Compound 21(d) (285.10 g, 0.736 mol) was combined withisopropyl acetate (1 L) in a heavy-walled Parr bottle. 10% Palladium oncarbon (16.51 g) was carefully wet with isopropyl acetate (1200 mL) andwashed into the Parr bottle. The reaction mixture was hydrogenated at0-50 psig of hydrogen pressure on a Parr shaker until hydrogen uptakeceased. The mixture was filtered through Celite™ and rinsed withisopropyl acetate (1 L). The filtrate was concentrated by rotaryevaporation, and the remaining wet solid was isolated.

The above reaction was repeated using 287.52 g (0.74 mol) of compound21(d), 16.67 g of 10% palladium on carbon and 1200 mL of isopropylacetate, and the products were combined and used directly in the nextstep.

f. Preparation of compound 21(f)(2-(4-fluoro-phenyl)-5-isopropoxy-6-methanesulfonylamino-benzofuran-3-carboxylicacid ethyl ester). Compound 21(e) (about 1.48 mol) was dissolved indichloromethane (5.6 L) and cooled in an ice/ethanol bath. Methanesulfonyl chloride (186.27 g, 1.63 mol) was added in one portion,followed by the dropwise addition of diisopropylethylamine (210.16 g,1.63 mol) over a 25-minute period. The reaction was allowed to warm toroom temperature, and was stirred for about 36 hours under nitrogen gas.The reaction was partitioned with water (2 L), the layers separated, andthe organic layer was rinsed with water (3×2 L). The combined aqueouslayers were back-extracted with dichloromethane (500 mL), and theorganic layers were combined. The organics were concentrated by rotaryevaporation. Ethanol was slowly added during the concentration, afterthe product began to precipitate. After the dichloromethane was removed,the mixture was diluted with t-butylmethyl ether (500 mL). The productwas isolated by filtration and air-dried to provide 603.1 g of a mixtureof product (90.8%) and disubstituted amine (8.9%).

¹H NMR in DMSO (300 MHz): 9.00 (s, 1H); 8.05 (m, 3H); 7.60 (s, 1H); 7.53(s, 1H); 7.39 (dd, J=8.8 & 8.8 Hz, 2H); 4.73 (septet, J=5.9 Hz, 1H);4.32 (q, J=7.0 Hz, 2H); 3.00 (s, 3H); 1.37 (d, J=5.9 Hz, 6H); 1.32 (t,J=7.0 Hz, 3H),

g. Preparation of compound 21(g)(2-(4-fluoro-phenyl)-5-isopropoxy-6-methanesulfonylamino-benzofuran-3-carboxylicacid). Compound 21(f) (570 g) was added to a solution of ethanol (6 L)and 1N NaOH (6 L). The solution was heated slowly to about 73° C. forseveral hours. Heat was then removed, and when the mixture reached about50° C., 6N HCl was added until approximately pH2 was obtained. Themixture was stirred for 15-minutes, and the solids were quickly isolatedby filtration and rinsed with 50/50 ethanol/water (500 mL), and thenwater (500 mL). The solid was dried in a vacuum oven to provide 513 g ofthe desired product.

¹H NMR in DMSO (300 MHz) of compound 21(g), prepared essentially asabove: 8.97 (s, 1H); 8.05 (m, 2H); 7.58 (s, 1H); 7.54 (s, 1H); 7.38 (dd,J=8.8 & 8.8 Hz, 2H); 4.69 (septet, J=5.9 Hz, 1H); 2.99 (s, 3H); 1.35 (d,J=5.9 Hz, 6H).

h. Preparation of compound 21(h)(2-(4-fluoro-phenyl)-5-isopropoxy-6-methanesulfonylamino-benzofuran-3-carboxylicacid methylamide). Compound 21(g) (1.39 kg, 3.4 mol, which can beprepared according to the previous step) was mixed with dichloromethane(18.9 kg), and stirred under nitrogen gas. The mixture was cooled tobelow 20° C., and 1,1′-carbonyldiimidazole (714 g, 4.40 mol) was addedin portions over about 15 to 30 minutes. The mixture was warmed to about30° and stirred for at least ninety minutes. Methylamine (2M in THF,72.9 kg, 6.8 mol) was added to the reaction over an about 45-minuteperiod, maintaining the temperature below 40° C. The reaction wasallowed to stir at about 30° C. to 40° C. for three hours. The reactionwas cooled to 20° C. and was quenched with water (6.8 kg). The mixturewas stirred and the layers were separated. The aqueous layer was rinsedwith dichloromethane (4.5 kg), and the first organic layer was washedwith water (2×6.8 kg). The aqueous layers were combined and backextracted with the second organic layer. The organic layers werefiltered, combined, and concentrated by atmospheric distillation of thevolatiles. Ethanol (3.4 L) was added and the mixture was cooled to lessthan 30° C. The solid was isolated by filtration, rinsed with ethanol(3.4 L, 190 proof), and dried to provide 1.35 kg (94%) of desiredproduct.

Example 22 and Example 23 Preparation of6-ethylamino-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylicacid methylamide and6-diethylamino-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylicacid methylamide

Diisopropylethylamine (407 μL, 2.34 mmol) and ethyl iodine (187 μL, 2.34mmol) were added to a solution of6-amino-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acidmethylamide, prepared according to Example 16 (200 mg, 584 μmol) in dryacetonitrile (8 mL). The reaction was monitored under analytical LC/MSconditions and quenched by addition of water (4 mL). After concentrationto dryness, the crude product was purified by preparative HPLC (reversephase C18, acetonitrile/water plus 0.1% acetic acid), affording 97 mg(45%) of the6-ethylamino-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylicacid methylamide and 63 mg (27%) of6-diethylamino-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylicacid methylamide.

Example 24 Preparation of2-(4-fluoro-phenyl)-5-isopropoxy-6-morpholin-4-yl-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 24(a)(6-bromo-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acid).Bromine (neat, 1.1 mL, 20.70 mmol) was added dropwise over 30 minutes toa stirred solution of compound 16(a) (5.0 g, 0.016 mol) in 1,4-dioxane(160 mL) in the presence of a 300-watt light. After stirring for anadditional 20 minutes, the reaction mixture was mixed with water andextracted with ethyl acetate. The organic phase was washed with waterand brine, dried over MgSO₄, and concentrated under reduced pressure toyield a yellow solid. The product was triturated with 30% ethyl acetatein hexanes to yield 4.1 g (66%) of the desired product as a white solid.

b. Preparation of compound 24(b)(6-bromo-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acidmethylamide). Benzotriazol-1-yloxytrispyrrolidinophosphoniumhexafluorophosphate (PyBop) (10.79 g, 20.76 mmol) and methylamine (43.0mL, 86 mmol) (2.0M solution in THF) were added to a solution of compound24(a), which can be prepared according to the preceding step, (6.8 g,17.3 mmol) in DMF (10.0 mL) under an argon atmosphere. After stirring atroom temperature for 12 hours, the reaction mixture was treated withwater and extracted with ethyl acetate. The organic layer was washedwith water and brine, dried over MgSO₄, and concentrated under reducedpressure. The crude product was purified by column chromatography(silica gel, 50 to 100% ethyl acetate in hexanes) to yield desiredproduct 6.5 g (92%) as a white solid.

c. Preparation of2-(4-fluoro-phenyl)-5-isopropoxy-6-morpholin-4-yl-benzofuran-3-carboxylicacid methylamide. Compound 24(b) (120 mg, 0.30 mmol),tris(dibenzylideneacetone)dipalladium (5.4 mg, 0.0059 mmol), and(2-dicyclohexylphosphino-2′-N,N-dimethylamino)-biphenyl (3.0 mg 2.4 mol%) were added to an oven-dried 100 mL round bottomed flask. The flaskwas sealed with a rubber septum, degassed and purged with argon.Morpholine (31 μl, 0.35 mmol) and lithium bis(trimethylsilyl amide) (650μl, 0.65 mmol, 1M solution in THF) were added to the reaction mixture.The septum was quickly removed, and a reflux condenser was placed on theflask. The reaction flask was degassed again and purged with argon. Thereaction mixture was then heated to 65° C. for 12 hours and cooled toroom temperature. 1M Hydrochloric acid (600 μl) was added, and thereaction mixture was stirred for 5 minutes, followed by passage througha small pad of Celite™. The filtrate was diluted with water andextracted with ethyl acetate. The organic layer was washed with waterand brine, dried over MgSO₄, and concentrated under reduced pressure.The crude product was purified by column chromatography (silica gel, 20to 40% ethyl acetate in hexanes) to provide 70 mg (57%) of the desiredproduct as a white solid.

Example 25 Preparation of5-methoxy-4-methyl-2-phenyl-benzofuran-3-carboxylic acid methylamide

a. Preparation of compound 25(a)(4-bromo-5-hydroxy-2-phenyl-benzofuran-3-carboxylic acid ethyl ester).Compound 2(a), which can be prepared according to Example 2 (450 mg,1.595 mmol) was dissolved in a mixture of CS₂:CH₃CN (3:1) (8.0 mL) underargon. The solution was cooled to 0° C., and N-bromosuccinimide (312 mg,1.755 mmol) was added in one portion. The reaction was stirred for 4hours at 0° C., and then warmed to room temperature. The solvent wasevaporated, and the residue was dissolved in ethyl acetate, washed withwater and brine, dried over MgSO₄, and concentrated under reducedpressure. The crude product was purified by HPLC (silica gel, elutingwith 10 to 100% ethyl acetate in hexanes to provide 396 mg (69%) of thedesired product.

b. Preparation of compound 25(b)(4-bromo-5-methoxy-2-phenyl-benzofuran-3-carboxylic acid ethyl ester).Potassium carbonate (365 mg, 2.638 mmol) and methyl iodide (1.3 mL, 21.1mmol) were added to a solution of compound 25(a) (380 mg, 1.055 mmol)dissolved in acetonitrile (5.0 mL), under an argon atmosphere. Afterstirring under reflux conditions for 4 hours, the reaction mixture wascooled to room temperature, diluted with water, and extracted with ethylacetate. The organic layer was washed with water and brine, dried overMgSO₄, and concentrated under reduced pressure to provide 385 mg (98%)of the desired product.

c. Preparation of compound 25(c)(5-methoxy-4-methyl-2-phenyl-benzofuran-3-carboxylic acid ethyl ester).Compound 25(b) (30 mg, 0.082 mmol) was mixed with Ag₂O (46.5 mg, 0.201mmol), methyl boronic acid (6.0 mg, 0.0884 mmol), K₂CO₃ (34.0 mg, 0.246mmol), 1,1-bis(diphenylphosphinoferrocene)dichloropalladium(II) complexwith dichloromethane (1:1) (Pd(dppf)Cl₂) (6.0 mg, 10 mol %), and THF(degassed, 1.0 mL) under argon atmosphere in a tube. The pressure tubewas sealed, and the reaction mixture was stirred at 80° C. for 12 hours,cooled to room temperature, and quenched with a mixture of 30% H₂O₂ (5mL) and 10% NaOH. The reaction mixture was diluted with water andextracted with ethyl acetate. The organic phase was washed with waterand brine, dried over MgSO₄, and concentrated under reduced pressure.The crude product was purified by reverse phase HPLC to provide 16.9 mg(64%) of the desired product.

d. Preparation of compound 25(d)(5-methoxy-4-methyl-2-phenyl-benzofuran-3-carboxylic acid). Compound25(c) (16.9 mg, 0.0545 mmol) was dissolved in ethanol (2.0 mL) and 12MNaOH (200 μl) was added. The reaction mixture was heated to 100° C. for6 hours and cooled to room temperature. The solvent was evaporated underreduced pressure. The residue was dissolved in water, acidified with 10%aqueous HCl, and extracted with ethyl acetate. The organic layer waswashed with water and brine, dried over MgSO₄, and concentrated underreduced pressure to provide 13.5 mg, (87%) of the desired product.

e. Preparation of 5-methoxy-4-methyl-2-phenyl-benzofuran-3-carboxylicacid methylamide. Bromo-tris-pyrrolidino-phosphonium hexafluorophosphate(PyBrop) (25.0 mg, 0.0526 mmol) and methylamine (0.5 mL, 2.0 M solutionin THF) were added to a solution of compound 25(d) (13.5 mg, 0.479 mmol)dissolved in DMF (1.0 mL) under an argon atmosphere. After stirring atroom temperature for 12 hours, the reaction mixture was treated withwater and extracted with ethyl acetate. The organic layer was washedwith water and brine, dried over MgSO₄, and concentrated under reducedpressure. The crude product was purified by column chromatography(silica gel, ethyl acetate/hexanes) to provide 9.0 mg (64%) of the titlecompound.

Example 26 Preparation of 5-cyano-2-phenyl-benzofuran-3-carboxylic acidmethylamide

a. Preparation of compound 26(a) (acetic acid4-cyano-2-phenylethynyl-phenyl ester). 1,4-Dioxane (2.5 mL, dry) wasadded to a stirred suspension of CuI (8.0 mg, 2 mol %) anddichlorobis(benzonitrile)palladium (II) (24 mg, 3 mol %) in a dryseptum-capped flask with constant purging of argon. Tri-t-butylphosphine(542 μl, 0.25M solution in 1,4-dioxane), diisopropyl amine (350 μl, 4.17mmol), acetic acid 2-bromo-4-cyano-phenyl ester (500 mg, 2.08 mmol), andphenyl acetylene (254 mg, 2.71 mmol) were added with syringes to thestirred reaction mixture. The reaction mixture was stirred for 6 hours,and then diluted with ethyl acetate and passed through small pad ofsilica gel. The filtrate was concentrated, and the crude product waspurified by column chromatography (silica gel, 5 to 20% ethyl acetate inhexanes) to provide 390 mg (72%) of the desired product.

b. Preparation of compound 26(b)(4-hydroxy-3-phenylethynyl-benzonitrile). Potassium carbonate (309 mg,2.24 mmol) was added to a solution of compound 26(a) (390 mg, 1.49 mmol)in methanol (10.0 mL). The reaction mixture was stirred at roomtemperature overnight, and then the solvent was evaporated under reducedpressure. The residue was treated with water and extracted with ethylacetate. The organic layer was washed with water and brine, dried overMgSO₄, and concentrated under reduced pressure. The crude product waspurified by column chromatography (silica gel, eluting with 5 to 25%ethyl acetate in hexanes) to provide 180 mg (55%) of the desiredproduct.

c. Preparation of compound 26(c)(5-cyano-2-phenyl-benzofuran-3-carboxylic acid methyl ester). Compound26(b) (100 mg, 0.4566 mmol) was mixed with thiourea (2.0 mg, 5 mol %),CBr₄ (378.5 mg, 1.141 mmol), cesium carbonate (445 mg, 1.367 mmol), PdI₂(8.2 mg, of 5 mol %) and methanol (2 mL). The reaction mixture wastreated with a stream of carbon monoxide gas at room temperature forfive minutes and at 45° C. for 10 minutes. Stirring was continued at 45°C. under a carbon monoxide atmosphere (balloon) overnight. The reactionmixture was then passed through a small pad of silica gel, rinsing withethyl acetate. The filtrate was concentrated, and the crude product waspurified by column chromatography (silica gel, eluting with 5-10% ethylacetate in hexanes) to provide 74 mg of a 60:40 mixture of compound26(c)(i) and 2-phenyl-benzofuran-5-carbonitrile.

d. Preparation of compound 26(d)(5-cyano-2-phenyl-benzofuran-3-carboxylic acid). The above mixture ofcompound 26(c) and 2-phenyl-benzofuran-5-carbonitrile (74 mg) wasdissolved in ethanol (2.0 mL) and treated with 12M NaOH (200 μl). Thereaction mixture was heated to 50° C. for 6 hours, then cooled to roomtemperature, and the solvent was concentrated under reduced pressure.The residue was dissolved in water, acidified with 10% HCl, andextracted with ethyl acetate. The organic layer was washed with waterand brine, dried over MgSO₄, and concentrated under reduced pressure.The crude product was purified by column chromatography (silica gel,eluting with 30 to 40% ethyl acetate/hexanes) to yield acid 30 mg (25%yield from steps c-d) of the desired product.

e. Preparation of 5-cyano-2-phenyl-benzofuran-3-carboxylic acidmethylamide. The target product (16.0 mg, 51%) was prepared essentiallyaccording to the general procedure described in Example 25, step e;however, compound 26(d) was used instead of compound 25(d).

Example 27 Preparation of5-isopropoxy-2-pyridin-4-yl-benzofuran-3-carboxylic acid methylamide

a. Preparation of compound 27(a) (4-isopropoxy-phenol). 2-Iodopropane(27.22 mL, 0.27 mol) was added to a stirred mixture of hydroquinone (30g, 0.27 mol) in ethanol (30 mL), and the reaction mixture was heated to60° C. Potassium hydroxide (15.3 g, 0.27 mol) was dissolved in water (50mL) and added dropwise to the reaction mixture over a one-hour period.After stirring at 60° C. for five hours, the mixture was cooled to roomtemperature, and the solvent was removed under reduced pressure. Theresidue was acidified with 6N HCl and extracted with ether. The organiclayer was washed with water and brine, dried with MgSO₄, andconcentrated. The crude product was purified by column chromatography(silica gel, eluting with 10 to 30% ethyl acetate/hexanes) to yield 20.3g (49%) of the desired product.

b. Preparation of compound 27(b) (2-bromo-4-isopropoxy-phenol).N-Bromosuccinimide (5.85 g, 0.033 mol) was added to a stirred solutionof compound 27(a) (5.0 g, 0.033 mol) in carbon disulfide (132 mL). Thereaction mixture was stirred at room temperature for 2 hours, and thenthe solvent was evaporated under reduced pressure to dryness. Theresidue was treated with water and extracted with ethyl acetate. Theorganic layer was washed with water and brine, dried with MgSO₄ andconcentrated. The crude product was purified by column chromatography(silica gel, eluting with 5 to 10% ethyl acetate/hexanes) to yield 4.65g (61%) of the desired product.

c. Preparation of compound 27(c) (acetic acid2-bromo-4-isopropoxy-phenyl ester). 4-Dimethylaminopyridine (catalytic)and triethyl amine (6.9 mL, 0.050 mol) were added to a stirred solutionof compound 27(b) (4.6 g, 0.02 mol) in dichloromethane (20 mL). Thereaction mixture was stirred for 10 minutes, and then acetic anhydride(4.5 mL, 0.48 mol) was added. After stirring for 4 hours, water wasadded to the reaction mixture. The mixture was extracted with ethylacetate, and the organic layer was washed with water and brine, driedwith MgSO₄, and concentrated. The crude product was purified by columnchromatography (silica gel, eluting with 0 to 10% ethyl acetate/hexanes)to yield 4.75 g (87%) of the desired product.

d. Preparation of compound 27(d) (4-trimethylsilanylethynyl-pyridine).Compound 27(d) (2.4 g, 53%) was prepared essentially according to thegeneral procedure described in Example 26, step a; however4-bromopyridine hydrochloride salt and (trimethylsilyl)acetylene wereused instead of acetic acid 2-bromo-4-cyano-phenyl ester and phenylacetylene.

e. Preparation of compound 27(e) (4-ethynyl-pyridine). Potassiumhydroxide (21.0 mg, 3.0 mol %) was added to a stirred solution ofcompound 27(d) (2.2 g, 0.0126 mmol) in degassed methanol (8.0 mL). Afterstirring for 30 minutes, water was added, and the mixture was extractedwith dichloromethane. The organic layer was washed with water and brine,dried with MgSO₄, and concentrated to yield 640 mg (53%) of the desiredproduct.

f. Preparation of compound 27(f) (acetic acid4-isopropoxy-2-pyridin-4-ylethynyl-phenyl ester). Compound 27(f) (564mg, 61%) was prepared essentially according to the general proceduredescribed in Example 26, step a; however compound 27(c) and compound27(e) were used instead of 2-bromo-4-cyano-phenyl ester and phenylacetylene.

g. Preparation of compound 27(g)(4-isopropoxy-2-pyridin-4-ylethynyl-phenol). Hydrazine (9.5 mL, 0.5 M inTHF) was added to a stirred solution of compound 27(f) (564 mg, 1.91mmol) in THF (3.0 mL). After stirring for 30 minutes, water was added,and the product was extracted with ethyl acetate. The organic layer waswashed with water (3×100 mL) and brine, dried with MgSO₄, andconcentrated to provide 470 mg (97%) of the desired product as a whitesolid.

h. Preparation of compound 27(h)(5-isopropoxy-2-pyridin-4-yl-benzofuran-3-carboxylic acid methyl ester).The intermediate compound (430 mg, 74%) was prepared essentiallyaccording to the general procedure described in Example 26, step c;however compound 27(g) was used instead of compound 26(b).

i. Preparation of 5-isopropoxy-2-pyridin-4-yl-benzofuran-3-carboxylicacid methylamide. Lithium hydroxide (540 mg) and water (1.0 mL) wereadded to compound 27(g) (200 mg, 0.644 mmol) dissolved in 1,4-dioxane(5.0 mL). The reaction mixture was stirred at 80° C. for 12 hours. Themixture was cooled to room temperature, and the solvent was concentratedunder reduced pressure. The residue was dissolved in water, brought topH 7.0 with 10% HCl, and extracted with ethyl acetate. The organic layerwas washed with water and brine, dried over MgSO₄, and concentratedunder reduced pressure to provide 130 mg (68%) of the acid.

The above acid (65 mg, 0.22 mmol),benzotriazol-1-yloxytrispyrrolidinophosphonium hexafluorophosphate(PyBOP) (148 mg, 0.284 mmol) was dissolved in DMF (0.5 mL) andmethylamine (2.2 mL, 2.0M solution in THF). After stirring for 12 hours,water was added, and the crude product was extracted with ethyl acetate.The organic layer was washed with water and brine, dried over MgSO₄, andconcentrated. The crude product was purified by column chromatography(silica gel, eluting with 0 to 5% methanol/ethyl acetate) to provide 65mg (96%) of the title compound.

Example 28 Preparation of6-(3,5-dimethyl-isoxazol-4-yl)-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 28(a)(2-(4-fluorophenyl)-5-methoxybenzofuran-3-carboxylic acid ethyl ester).Compound 21(b) (50.0 g, 0.167 mol, which can be prepared according tothe general procedure described in Example 21) was dissolved inanhydrous 1-methyl-2-pyrrolidinone (176 mL) under argon with mechanicalstirring. Once homogeneous, cesium carbonate (108.8 g, 0.334 mol) wasadded portion wise over 15 minutes. Methyl iodide (32.2 mL, 0.516 mol)was added over 5 minutes. The reaction was heated to 50° C. for 18hours, then cooled to room temperature, diluted with concentratedammonium hydroxide (39 mL), and stirred for 30 minutes. The mixture wasdiluted with heptane (1000 mL) and washed with water (3×1000 mL). Thecombined organics were dried with magnesium sulfate and evaporated todryness. The resulting solid was stirred in hexanes for 18 hours,filtered, and dried. Since the reaction was incomplete (by proton NMR),the isolated solid was resubjected to anhydrous 1-methyl-2-pyrrolidinone(176 mL). Once homogeneous, cesium carbonate (40.0 g, 0.123 mol) andmethyl iodide (20.0 mL, 0.321 mol) were added. The reaction was againheated to 50° C. for 18 hours, cooled to room temperature, diluted withammonium hydroxide (24 mL), and stirred for 30 minutes. The mixture wasdiluted with water (1000 mL) and extracted with t-butylmethyl ether(3×300 mL). The combined organics were washed with water (300 mL) anddried with magnesium sulfate. After the solvent was evaporated, theproduct was crystallized from hot n-heptane, to provide 32.1 g (61%) ofthe desired product as a tan solid.

b. Preparation of compound 28(b)(2-(4-fluorophenyl)-5-methoxybenzofuran-3-carboxylic acid). Compound28(a) (32 g, 0.102 mol) and potassium hydroxide (6.3 g, 0.112 mol) werecombined in ethanol (80 mL) and water (80 mL). The reaction mixture wasgently refluxed overnight. TLC analysis showed reaction to beincomplete, so an additional amount of potassium hydroxide (2.0 g, 0.035mol) was added. After one hour, the solvent was evaporated to halfvolume. The solution was diluted with water (400 mL) and extracted withethyl acetate (2×300 mL). The aqueous solution was acidified with 3MHCl, and the resulting precipitate was filtered, washed with water, anddried to provide 28.9 g (99%) of the product as a white solid.

c. Preparation of compound 28(c)(6-bromo-2-(4-fluorophenyl)-5-methoxybenzofuran-3-carboxylic acid).Compound 28(b) (28.9 g, 0.101 mol) was dissolved in anhydrous1,4-dioxane (725 mL) under argon. The resulting solution was degassedwith argon through a gas dispersion tube for 10 minutes. Bromine (8.8mL, 0.170 mol) was added dropwise via syringe over 45 minutes. Onceaddition was complete, the reaction was stirred at room temperature for30 minutes. An additional amount of bromine (0.5 mL, 0.01 mol) was addeddropwise over 5 minutes. The mixture was diluted with ethyl acetate(1800 mL), washed with water (5×350 mL), and dried with magnesiumsulfate. The solvent was evaporated, and the remaining solid wasdissolved in ethyl acetate (250 mL). The solvent was again removed byevaporation. The process of dissolving in ethyl acetate, followed byevaporation was repeated until the solvent was free of color. Theresulting solid was sonicated in a 80/20 mixture of hexane/ethyl acetate(500 mL), and the crude product was isolated via filtration. Thefiltrate was concentrated, and the resulting solids were sonicated in an80/20 mixture of hexane/ethyl acetate (300 mL). The solid was isolatedvia filtration and combined with the crude product. The solids werewashed with a 95/5 mixture of hexane/ethyl acetate (100 mL) and thenwith hexanes. The solid was dried under vacuum dry, to provide 28.4 g(77%) of the desired product as a tan solid.

d. Preparation of compound 28(d)(6-bromo-2-(4-fluorophenyl)-5-methoxybenzofuran-3-carboxylic acid methylester). Milled potassium carbonate (40.6 g, 0.294 mol) and methyl iodide(92.0 mL, 1.47 mol) were added to a stirring solution of compound 28(c)(53.6 g, 0.147 mol, which can be prepared according to the previousstep) dissolved in 1-methyl-2-pyrrolidinone (1000 mL). The reactionmixture was stirred at 50° C. for 18 hours. Upon cooling, the reactionwas diluted with water (2200 mL) and extracted with ethyl acetate (5×600mL). The organics were combined, washed with water (3×1000 mL), anddried with magnesium sulfate. The solvent was evaporated, and the crudeproduct was purified by sonicating in a 90/10 mixture of hexane/ethylacetate for 1 hour. The solid was removed by filtration, washed withhexanes and dried under vacuum, to provide 47.4 g (125 mol, 85%) of thedesired product as a white solid.

e. Preparation of compound 28(e)(6-(3,5-dimethylisoxazol-4-yl)-2-(4-fluorophenyl)-5-methoxybenzofuran-3-carboxylicacid methyl ester). Compound 28(d) (12.0 g, 0.0316 mol) was dissolved intoluene (900 mL), ethanol (420 mL), and water (24 mL), under argon. Theresulting solution was degassed with argon through a gas dispersion tubefor 10 minutes. Sodium carbonate (8.37 g, 79.0 mmol),3,5-dimethylisoxazole-4-boronic acid (6.69 g, 47.5 mmol), andtetrakis-triphenylphosphine-palladium(0) (1.83 g, 1.58 mmol) were added,and the reaction was gently refluxed for 21 hours. The solvent wasevaporated, and the reaction was diluted with ethyl acetate (500 mL) andwater (300 mL). The layers were separated, and the organic phase waswashed with water (2×500 mL). The aqueous washings were combined andextracted with ethyl acetate (300 mL). The organics were combined,washed with brine, and dried with magnesium sulfate. The solvent wasevaporated, and the crude product was purified by flash chromatography(silica gel, ethyl acetate/hexane gradient) providing 10.4 g (83%) ofthe desired product as an off-white solid.

f. Preparation of compound 28(f)(6-(3,5-dimethylisoxazol-4-yl)-2-(4-fluorophenyl)-5-methoxybenzofuran-3-carboxylicacid). Compound 28(e) (10.4 g, 26.3 mmol) and potassium hydroxide (5.90g, 105 mmol) were combined in ethanol (500 mL) and water (500 mL) andgently refluxed for 4 hours. After cooling, two-thirds of the solventwas evaporated, and the solution was diluted with water (300 mL). Thesolution was filtered through a pad of Celite™ 503 to remove a smallamount of palladium residue from the previous step. The solution wasacidified with 6M HCl, and the precipitate was filtered, washed withwater and hexanes, and partially dried under vacuum to provide thedesired product as a white solid. The unpurified product was useddirectly in the next step.

g. Preparation of6-(3,5-dimethylisoxazol-4-yl)-2-(4-fluorophenyl)-5-methoxybenzofuran-3-carboxylicacid methylamide. Compound 28(f) (10.0 g, 0.0262 mol),benzotriazol-1-yloxytrispyrrolidinophosphonium hexafluorophosphate(PyBOP) (16.4 g, 0.0315 mol), and methylamine (131 mL, 2M in THF, 0.262mol) were combined with DMF (16 mL). The reaction was stirred at roomtemperature under argon for 18 hours. The solvent was evaporated, andthe resulting solids were dissolved in ethyl acetate (250 mL) and water(300 mL). The layers were separated, and the aqueous phase was extractedwith ethyl acetate (4×200 mL). The organics were combined, washed withwater (3×150 mL) and brine (300 mL), and dried with magnesium sulfate.The solvent was evaporated, and the crude product was mixed with a 90/10mixture of hexane/ethyl acetate (100 mL). The mixture was filtered, andthe solids were washed with hexane and dried under vacuum to provide thedesired product 8.16 g (79%) as a white solid.

The crude product was later purified via crystallization (hot ethanoland water) after being combined with several other batches of compound,to provide the title compound as white needles.

Example 29 Preparation of2-(4-fluoro-phenyl)-6-(methanesulfonyl-methyl-amino)-5-methoxy-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 29(a)(2-(4-fluoro-phenyl)-5-hydroxy-6-methanesulfonylamino-benzofuran-3-carboxylicacid methylamide). Boron trichloride (60 mL of 1M dichloromethane) wasadded for 10 minutes to2-(4-fluoro-phenyl)-5-isopropoxy-6-methanesulfonylamino-benzofuran-3-carboxylicacid methylamide (7.10 g, 16.9 mmol, which can be prepared according toone of the procedures described in Example 21), in dichloromethane (200mL). The mixture was stirred for 20 hours, and then carefully quenchedwith 1N HCl (10 mL). An additional amount of 4N HCl (100 mL) was added,and the reaction mixture was stirred for 24 hours. The precipitatedsolid was filtered off, washed with water, dried, and triturated withethyl acetate/hexanes to provide 6.39 g (100%) of the desired product asa white solid.

b. Preparation of2-(4-fluoro-phenyl)-6-(methanesulfonyl-methyl-amino)-5-methoxy-benzofuran-3-carboxylicacid methylamide. Potassium carbonate (0.30 g, 2.17 mmol) andiodomethane (0.10 mL, 1.61 mmol) were added to a solution of compound29(a) (0.11 g, 0.291 mmol, which can be prepared according the previousstep) in 2-butanone (20 mL). The reaction mixture was refluxed for 1-2hours and then cooled to room temperature and concentrated. The crudeproduct was dissolved in ethyl acetate and washed with 1M hydrochloricacid. The organic layer was concentrated, and the product was purifiedby flash chromatography (silica gel, ethyl acetate/hexanes gradient) toprovide 73 mg (62%) of the desired product as a white solid.

Example 30 Preparation of2-(4-fluoro-phenyl)-5-(4-methoxy-benzyloxy)-6-morpholin-4-yl-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 30 (a)(2-(4-fluoro-phenyl)-5-hydroxy-6-morpholin-4-yl-benzofuran-3-carboxylicacid methylamide). Boron trichloride (1M solution in xylenes, 5.0 mL,5.0 mmol) was added to a solution of2-(4-fluoro-phenyl)-5-isopropoxy-6-morpholin-4-yl-benzofuran-3-carboxylicacid methylamide (0.71 g, 1.7 mmol, which can be prepared according toExample 24, above), dissolved in dichloromethane (30 mL). The reactionmixture was refluxed for 30 minutes, cooled to room temperature,quenched with 1M hydrochloric acid (10 mL) and stirred for 1 hour. Theorganics were removed by evaporation, and a saturated solution of sodiumbicarbonate was added until pH=8-9. The product was extracted with ethylacetate and purified via column chromatography (dry loading onto silicagel, ethyl acetate/hexanes gradient) to provide 0.53 g (84%) of thedesired product.

b. Preparation of2-(4-fluoro-phenyl)-5-(4-methoxy-benzyloxy)-6-morpholin-4-yl-benzofuran-3-carboxylicacid methylamide. Potassium carbonate (0.40 g, 2.89 mmol) and4-methoxybenzyl chloride (0.20 mL, 1.47 mmol) were added to compound30(a) (0.311 g, 0.840 mmol) dissolved in acetonitrile (20 mL). Thereaction mixture was refluxed for 12 hours, cooled to room temperatureand concentrated. The crude product was dissolved in ethyl acetate andwashed with 1M hydrochloric acid. The organic layer was concentrated,and the product was purified by flash chromatography (silica gel, ethylacetate/hexanes gradient) to provide 296 mg (72%) of the desired productas a white solid.

Example 31 Preparation of2-(4-fluoro-phenyl)-6-[methanesulfonyl-(4-methoxy-benzyl)-amino]-5-(4-methoxy-benzyloxy)-benzofuran-3-carboxylicacid methylamide

Potassium carbonate (0.040 g, 0.285 mmol) and 4-methoxybenzyl chloride(0.026 mL, 0.190 mmol) were added to a solution of compound 29(a) (0.036g, 0.095 mmol, which can be prepared according to Example 29, step aabove), dissolved in 2-butanone (10 mL). The reaction was stirred at 20°C. for 72 hours. The reaction mixture was concentrated, and the crudeproduct was dissolved in ethyl acetate and washed with 1M hydrochloricacid. The organic layer was concentrated, and the product was purifiedby flash chromatography (silica gel, ethyl acetate/hexanes gradient) toprovide 34 mg (58%) of the desired product as a white solid.

Example 32 Preparation of5-ethoxy-6-(ethyl-methanesulfonyl-amino)-2-(4-fluoro-phenyl)-benzofuran-3-carboxylicacid methylamide

Potassium carbonate (0.10 g, 0.72 mmol) and iodoethane (0.10 mL, 1.25mmol) were added to a solution of compound 29(a) (0.036 g, 0.095 mmol,which can be prepared according to Example 29 step a, above), dissolvedin 2-butanone (15 mL), and the reaction mixture was stirred at 20° C.for 72 hours. The reaction mixture was concentrated, and the crudeproduct was dissolved in ethyl acetate and washed with 1M hydrochloricacid. The organic layer was concentrated, and the product was purifiedby flash chromatography (silica gel, ethyl acetate/hexanes gradient) toprovide 25 mg (61%) of the title compound as a white solid.

Example 33 Preparation of2-(4-fluoro-phenyl)-6-morpholin-4-yl-5-(thiazol-2-ylmethoxy)-benzofuran-3-carboxylicacid methylamide

a. Preparation of (2-chloromethyl-thiazole). Thionyl chloride (2 mL,27.4 mmol) was added to 2-hydroxymethyl thiazole (0.15 g, 1.30 mmol)dissolved in dichloromethane (2 mL). The reaction mixture was heated toreflux for 3 seconds and then cooled and stirred for 20 minutes at roomtemperature. The reaction was concentrated, dried on high vacuum pumpand used immediately in the following step.

b. Preparation of2-(4-fluoro-phenyl)-6-morpholin-4-yl-5-(thiazol-2-ylmethoxy)-benzofuran-3-carboxylicacid methylamide. Potassium carbonate (0.10 g, 0.72 mmol) and2-chloromethyl-thiazole (0.021 g, 0.157 mmol) were added to a solutionof compound 30(a) (0.050 g, 0.135 mmol, which can be prepared accordingto Example 30, step (a) above) dissolved in acetonitrile (15 mL). Thereaction was refluxed for 2 hours and then warmed at 60° C. for 16hours. The reaction was cooled and concentrated, and crude product wasdissolved in ethyl acetate and washed with 1M hydrochloric acid. Theorganic layer was concentrated, and the product was purified by flashchromatography (silica gel, ethyl acetate/hexanes gradient) to give 37mg (59%) of the desired product as a white solid.

Example 34 Preparation of2-(4-fluoro-phenyl)-5-isopropoxy-6-[methanesulfonyl-(2-oxo-propyl)-amino]-benzofuran-3-carboxylicacid methylamide

2-(4-Fluoro-phenyl)-5-isopropoxy-6-methanesulfonylamino-benzofuran-3-carboxylicacid methylamide (0.093 g, 0.221 mmol, which can be prepared accordingto one of the procedures described in Example 21) was dissolved in2-butanone (20 mL). Potassium carbonate (0.20 g, 1.45 mmol) andchloroacetone (0.10 mL, 1.25 mmol) were added at 20° C. The reactionmixture was refluxed for 2 hours, cooled to room temperature andconcentrated. The crude product was dissolved in ethyl acetate andwashed with 1M hydrochloric acid. The organic layer was concentrated,and the product was purified by flash chromatography (silica gel, ethylacetate/hexanes gradient) to provide 99 mg (94%) of the title compoundas a white solid

Example 35 Preparation of2-(4-fluoro-phenyl)-6-morpholin-4-yl-5-(thiazol-4-ylmethoxy)-benzofuran-3-carboxylicacid methylamide

Potassium carbonate (0.200 g, 1.45 mmol) and 4-(chloromethyl)thiazolehydrochloride (0.100 g, 0.588 mmol) were added to a solution of compound30(a) (0.100 g, 0.270 mmol, which can be prepared according to Example30, step a above dissolved in 2-butanone (15 mL). The reaction wasrefluxed for 16 hours and then cooled to room temperature. The mixturewas concentrated, and the residue was dissolved in ethyl acetate andwashed with water. The organic layer was concentrated, and the productwas purified via column chromatography (dry loading onto silica gel,ethyl acetate/hexanes gradient, followed by 1% methanol/ethyl acetate)to provide the crude product. The solid was triturated with ethylacetate, filtered, and dried on high vacuum pump to provide 45 mg (36%)of the title compound as a white solid.

Example 36 Preparation of2-(4-fluoro-phenyl)-5-isopropoxy-6-(methanesulfonyl-thiazol-4-ylmethyl-amino)-benzofuran-3-carboxylicacid methylamide

Potassium carbonate (0.050 g, 0.357 mmol) followed by4-(chloromethyl)thiazole hydrochloride (0.041 g, 0.238 mmol) were addedto a solution of2-(4-fluoro-phenyl)-5-isopropoxy-6-methanesulfonylamino-benzofuran-3-carboxylicacid methylamide (0.050 g, 0.119 mmol, which can be prepared accordingto one of the procedures described in Example 21 above), dissolved inacetonitrile (10 mL). The reaction was refluxed for 1 hour with novisible product formation observed by TLC, so potassium iodide (0.020 g,0.120 mmol) was added to the reaction. The mixture was refluxed for anadditional 2 hours, and then cooled to room temperature. The reactionmixture was concentrated, and the residue was dissolved in ethyl acetateand washed with water. The product was concentrated and purified byflash chromatography (silica gel, ethyl acetate/hexanes gradient) toprovide 30 mg (48%) of the desired product as a white solid.

Example 37 Preparation of2-(4-fluoro-phenyl)-6-(5-hydroxymethyl-isoxazol-3-yl)-5-isopropoxy-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 37(a)(2-(4-fluoro-phenyl)-6-formyl-5-isopropoxy-benzofuran-3-carboxylic acidethyl ester). Hexamethylenetetramine (3.07 g, 21.9 mmol) and compound6(c) (5.0 g, 14.6 mmol, which can be prepared according to Example 6,step c above), were dissolved in trifluoroacetic acid (10 mL). Thereaction mixture was heated to 80° C. until the reaction appeared to be80% complete by TLC. The reaction mixture was cooled to roomtemperature, concentrated in vacuo, and partitioned between ethylacetate and water. The aqueous phase was washed with ethyl acetate, andthen the combined organic layers were washed with brine, dried (MgSO₄),and concentrated in vacuo. Purification by column chromatography (silicagel, ethyl acetate/hexanes gradient) provided 2.39 g (44%) of thedesired product as a white solid.

b. Preparation of compound 37(b)(2-(4-fluoro-phenyl)-6-(hydroxyimino-methyl)-5-isopropoxy-benzofuran-3-carboxylicacid ethyl ester). To a solution of compound 37(a) (1.23 g, 3.32 mmol)in ethanol (10 mL) and THF (25 mL) was added sodium acetate trihydrate(0.497 g, 3.65 mmol) in water (10 mL), followed by hydroxylaminehydrochloride (0.254 g, 3.65 mmol). The reaction mixture was gentlywarmed in a hot water bath, then allowed to cool slowly to ambienttemperature. The reaction was concentrated in vacuo and partitionedbetween ethyl acetate and water. The aqueous phase was washed with ethylacetate, and then the combined organic layers were washed with brine,dried (MgSO₄) and concentrated in vacuo to provide 1.44 g (>100%) of thedesired product. The product was taken on to the next step withoutfurther purification.

c. Preparation of compound 37(c)(2-(4-fluoro-phenyl)-5-isopropoxy-6-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-benzofuran-3-carboxylicacid ethyl ester). Compound 37(b) (0.300 g, 0.778 mmol) in chloroform (7mL) was added dropwise to a solution of N-chlorosuccinimide (0.104 g,0.778 mmol) and pyridine (catalytic) in chloroform (3 mL). The reactionmixture was heated to 50° C. for 4 hours then cooled to ambienttemperature. Triethylamine (0.219 mL, 1.55 mmol), and thentetrahydro-2-(2-propynyloxy)-2H-pyran (0.108 mL, 0.778 mmol) were added.The reaction was warmed to 70° C. for 16 hours, cooled to ambienttemperature, diluted with dichloromethane, and washed with 1 M HCl andbrine, dried (MgSO₄) and concentrated in vacuo. Purification by columnchromatography (silica gel, ethyl acetate/hexanes gradient) provided0.22 g (54%) of the desired product as a white solid.

d. Preparation of compound 37(d)(2-(4-fluoro-phenyl)-6-(5-hydroxymethyl-isoxazol-3-yl)-5-isopropoxy-benzofuran-3-carboxylicacid ethyl ester). Pyridinium p-toluenenesulfonate (7 mg, 0.028 mmol)was added to a solution of compound 27(c) (0.15 g, 0.28 mmol) in ethanol(5 mL) and THF (5 mL). After stirring at room temperature for 4 days, a1/1 mixture of ethanol/THF (10 mL) and an additional amount ofpyridinium p-toluenenesulfonate (7 mg, 0.028 mmol) were added. Thereaction mixture was warmed to 50° C. for 30 minutes, then cooled toroom temperature and concentrated in vacuo. The residue was partitionedbetween ethyl acetate and water. The aqueous phase was washed with ethylacetate, and the combined organic layers were washed with brine, dried(MgSO₄) and concentrated in vacuo to provide 0.13 g (100%) of thedesired product.

e. Preparation of compound 37(e)(2-(4-fluoro-phenyl)-6-(5-hydroxymethyl-isoxazol-3-yl)-5-isopropoxy-benzofuran-3-carboxylicacid). Potassium hydroxide solution (4N, 0.18 mL, 0.74 mmol) was addedto a suspension of compound 37(d) (0.13 g, 0.29 mmol) in ethanol (1 mL).The reaction mixture was stirred for 16 hours at room temperature,warmed to reflux for ½ hour, then cooled to room temperature. Themixture was neutralized with 4M HCl_((aq)) (0.18 mL, 0.74 mmol),filtered, and washed with ethanol/water (1/1, 2 mL). The mother liquorwas extracted with ethyl acetate (2×), washed with brine, dried (MgSO₄)and concentrated in vacuo. Both residues were combined and purified bycolumn chromatography (silica gel, 99/1 ethyl acetate/acetic acid) toprovide 0.078 g (65%) of the desired product.

f. Preparation of2-(4-fluoro-phenyl)-6-(5-hydroxymethyl-isoxazol-3-yl)-5-isopropoxy-benzofuran-3-carboxylicacid methylamide. 4-Methylmorpholine (23 μL, 0.210 mmol) followed byisobutylchloroformate (27 μL, in 2 mL THF, 0.210 mmol) were added to anice cooled solution of compound 27(e) (0.078 g, 0.190 mmol) in THF (5mL). The reaction mixture was stirred for 5 minutes, then methyl amine(2.0M in THF, 0.19 mL, 0.38 mmol) was added. The reaction was allowed tocome to room temperature and stirred for 16 hours. The mixture was thenpartitioned between ethyl acetate and water. The layers were separated,and the aqueous layer was washed with ethyl acetate (2×). The combinedorganic layers were washed with brine, dried (MgSO₄) and concentrated invacuo. Crystallization from ethyl acetate provided 10 mg (12%) of thetitle compound.

Example 38 Preparation of5-ethoxy-2-(4-fluoro-phenyl)-6-(methanesulfonyl-methyl-amino)-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 38(a)(5-(tert-butyl-dimethyl-silanyloxy)-2-(4-fluoro-phenyl)-6-methanesulfonylamino-benzofuran-3-carboxylicacid methylamide). A mixture of compound 29(a) (6.39 g, 16.9 mmol, whichcan be prepared according to Example 29, step a above), imidazole (5.00g, 73.5 mmol) and tert butyldimethylsilyl chloride (5.00 g, 33.2 mmol)in acetonitrile (70 mL) was stirred for 20 hours. The solvent wasremoved in vacuo, and the crude product was dissolved in 1N HCl andextracted with ethyl acetate. The combined organic layers wereconcentrated in vacuo, then purified by column chromatography (silicagel, ethyl acetate) to provide 7.20 g (87%) of the desired product as awhite solid.

b. Preparation of compound 38(b)(5-(tert-butyl-dimethyl-silanyloxy)-2-(4-fluoro-phenyl)-6-(methanesulfonyl-methyl-amino)-benzofuran-3-carboxylicacid methylamide). A solution compound 38(a) (5.50 g, 11.2 mmol),potassium carbonate (8.0 g, 58 mmol), and iodomethane (17 g, 0.12 mol)in acetonitrile (120 mL) was stirred at 20° C. for 20 hours, then pouredinto 1N HCl (100 mL). The organic solvents were removed in vacuo, andthe aqueous residue was extracted with ethyl acetate. The combinedorganic layers were concentrated in vacuo, and the resulting solid wastriturated with ethyl acetate/hexanes to give 5.60 g (99%) of thedesired product as a white solid.

c. Preparation of compound 38(c)(2-(4-fluoro-phenyl)-5-hydroxy-6-(methanesulfonyl-methyl-amino)-benzofuran-3-carboxylicacid methylamide). A solution of compound 38(b) (7.80 g, 15.4 mmol,which can be prepared according to the previous step) in THF (100 mL)was treated with a 1M solution of tetrabutylammonium fluoride (16 mL, 16mmol) in THF. After 1 hour the solvent was removed in vacuo, and thecrude product was dissolved in 1N HCl and extracted with ethyl acetate.The combined organic layers were concentrated in vacuo, and theresulting solid was triturated with ethyl acetate/hexanes to give 5.61 g(99%) of the desired product as a white solid.

d. Preparation of5-ethoxy-2-(4-fluoro-phenyl)-6-(methanesulfonyl-methyl-amino)-benzofuran-3-carboxylicacid methylamide. A solution of compound 38(c) (0.600 g, 1.53 mmol),potassium carbonate (0.58 g, 4.2 mmol) and iodoethane (1.00 g, 6.41mmol) in acetonitrile (30 mL) was stirred at reflux for 3 hours. Thesolvent was removed in vacuo, and the crude product was dissolved in 1NHCl and extracted with ethyl acetate. The combined organic layers wereconcentrated in vacuo, and the resulting solid was recrystallized fromabsolute ethanol. The precipitated solid was filtered and dried toprovide 0.54 g (84%) of the title compound as a white solid.

Example 39 Preparation of4-[2-(4-fluoro-phenyl)-6-(methanesulfonyl-methyl-amino)-3-methylcarbamoyl-benzofuran-5-yloxymethyl]-2-hydroxy-benzoicacid

a. Preparation of compound 39(a)(2,2,7-trimethyl-benzo[1,3]dioxin-4-one). 4-(Dimethylamino)pyridine(DMAP) (0.40 g, 3.29 mmol) and acetone (6.27 mL, 85.44 mmol) were addedto a solution of 4-methylsalicylic acid (10.0 g, 65.72 mmol) in1,2-dimethoxyethane (DME) (50 mL). Thionyl chloride (6.7 mL, 92.01 mmol)was dissolved in DME (5 mL) and added slowly to the reaction mixture.The reaction was stirred at room temperature for 36 hours. The mixturewas concentrated, and the crude product was dissolved in ethyl acetateand washed with water. The organics were concentrated, and the productwas purified by flash chromatography (silica gel, ethyl acetate/hexanesgradient) to provide 1.40 g (11%) of the desired product as a yellowsolid.

b. Preparation of compound 39(b)(7-bromomethyl-2,2-dimethyl-benzo[1,3]dioxin-4-one). To a solution ofcompound 39(a) (0.67 g, 3.49 mmol, which can be prepared according tothe previous step), in carbon tetrachloride (15 mL) was addedN-bromosuccinimide (0.74 g, 4.18 mmol) and benzoyl peroxide (0.068 g,0.279 mmol). The reaction was refluxed and irradiated with a heat lampfor 5 hours. The reaction was then cooled, and a solid was filteredaway. The filtrate was concentrated, dissolved in ethyl acetate andwashed with water. The organic layer was concentrated, and the productwas purified by flash chromatography (silica gel, ethyl acetate/hexanegradient) to provide 175 mg (19%) of the desired product as a whitesolid.

c. Preparation of compound 39(c)(5-(2,2-dimethyl-4-oxo-4H-benzo[1,3]dioxin-7-ylmethoxy)-2-(4-fluoro-phenyl)-6-(methanesulfonyl-methyl-amino)-benzofuran-3-carboxylicacid methylamide). Potassium carbonate (0.19 g, 1.38 mmol) and compound39(b) (0.25 g, 0.917 mmol) were added to a solution of compound 38(d)(0.18 g, 0.459 mmol, which can be prepared according to Example 38 stepd above), in acetonitrile (15 mL). The reaction mixture was refluxed for4 hours and then concentrated in vacuo. The crude product was dissolvedin ethyl acetate and washed with water. The organic layer wasconcentrated to a solid, which was triturated in 20% ethylacetate/hexanes, filtered, and dried to provide 240 mg (90%) of thedesired product as an off-white solid.

d. Preparation of4-[2-(4-fluoro-phenyl)-6-(methanesulfonyl-methyl-amino)-3-methylcarbamoyl-benzofuran-5-yloxymethyl]-2-hydroxy-benzoicacid. LiOH monohydrate (0.015 g, 0.343 mmol) was added to a suspensionof compound 39(c) (0.10 g, 0.172 mmol) in water/THF (10 mL/10 mL). Thereaction was stirred at room temperature for 4 hours. The THF wasremoved by rotary evaporation, and 1M HCl was added until an acidic pHwas reached. The precipitate was filtered and dried to provide 65 mg(70%) of the title compound as an off-white solid.

Example 40 Preparation of2-(4-fluoro-phenyl)-6-(5-hydroxymethyl-isoxazol-3-yl)-5-methoxy-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 40(a). ((2,5-dihydroxy-phenyl)-acetic acidmethyl ester). A solution of 5-hydroxy-3H-benzofuran-2-one (10.8 g, 71.9mmol) and Amberlyst®-15 (8.00 g) in dry methanol (25 mL) was stirred at22° C. for 72 hours. The reaction mixture was filtered through a pad ofCelite™ 503 before evaporation of the solvent. The resulting solid waspurified by flash column chromatography (silica gel, 20:80 ethylacetate/hexanes) to provide 12.84 g (98%) of the desired product as awhite solid.

b. Preparation of Compound 40(b).

A solution of 4-fluoro-benzoyl chloride (4.20 mL, 35.7 mmol) indichloromethane (10 mL) was added dropwise to a solution of compound125(a) (3.00 g, 16.5 mmol) and triethylamine (5.00 mL, 35.9 mmol) indichloromethane (70 mL) at 0° C. over 15 minutes. The reaction mixturewas stirred for 18 hours at 22° C., and then concentrated, diluted with1N HCl (100 mL) and extracted with ethyl acetate. The organic layer wasconcentrated to a crude oil, which was purified by flash columnchromatography (silica gel, ethyl acetate/hexanes gradient) to provide6.81 g (97%) of the desired compound as a white solid.

c. Preparation of compound 40(c)(3-(4-fluoro-benzoyl)-5-hydroxy-3H-benzofuran-2-one). Sodium hydride(95% in oil, 0.123 g, 5.13 mmol) was suspended in dry THF (0 mL) at 0°C., and compound 125(b) (1.05 g, 2.46 mmol) was added in one portion.The reaction mixture was stirred at 22° C. for 24 hours. After carefullyquenching with water, the reaction mixture was diluted with ethylacetate and extracted with 1N HCl and brine, then concentrated to give adark oil. The crude oil was purified by flash column chromatography(silica gel, 60% ethyl acetate/hexanes) to provide 0.74 g (100%) of thedesired compound.

d. Preparation of compound 40(d)(2-(4-fluoro-phenyl)-5-hydroxy-benzofuran-3-carboxylic acid ethylester). A solution of compound 40(c) (0.74 g, 2.46 mmol) in dry methanol(50 mL) was treated with concentrated sulfuric acid (0.2 mL), and themixture was refluxed for 25 hours. The reaction mixture wasconcentrated, and the resulting solid was purified by flash columnchromatography (silica gel, 10% ethyl acetate/hexanes) to provide 0.580g (78%) of the desired product as a white solid.

e. Preparation of compound 40(e)(2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acid ethylester). The intermediate compound was prepared essentially according tothe general procedure described in Example 12, step b above; however,compound 40(d) was used instead of the mixture of compounds 12(a)(i) and12(a)(ii).

f. Preparation of compound 40(f)(2-(4-fluoro-phenyl)-6-formyl-5-methoxy-benzofuran-3-carboxylic acidethyl ester). Titanium tetrachloride, 99% (15.4 mL, 140 mmol) was addedto a solution of a,a-dichloromethylmethyl ether (6.45 mL, 71.0 mmol) indichloromethane (100 mL) at 0° C. under an argon atmosphere. After theaddition was complete, compound 40(e) (20.0, 63.6 mmol) dissolved indichloromethane (75 mL) was added dropwise to the solution. One halfhour after the addition was complete, the reaction was cooled in anice-bath, and water (100 mL) was added dropwise. The reaction wasdiluted with dichloromethane until homogenous. The layers wereseparated, and the organic layer was washed with 3M HCl (1×100 mL) andbrine (1×100 mL), dried over MgSO₄, filtered and concentrated in vacuo.The residue was dissolved in ethyl acetate (1.3 L) and enough chloroformto bring everything into solution. The solution was filtered through aplug of Florisil®, concentrated in vacuo, and purified viacrystallization from ethyl acetate to provide 5.90 g (27%) of thedesired product.

g. Preparation of compound 40(g)(2-(4-fluoro-phenyl)-6-(hydroxyimino-methyl)-5-methoxybenzofuran-3-carboxylic acid ethyl ester). To a suspension of compound40(f) (3.29 g, 9.61 mmol) in THF (200 mL) was added sodium acetatetrihydrate (1.44 g, 10.6 mmol) in water (20 mL), then hydroxylaminehydrochloride (0.73 g, 10.6 mmol). After 1 hour, the reaction wasconcentrated in vacuo, and the residue was suspended in water. The solidwas filtered to yield 3.20 g (93%) of the desired product. The productwas taken on to the next step without further purification.

h. Preparation of compound 40(h)(2-(4-fluoro-phenyl)-5-methoxy-6-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-benzofuran-3-carboxylicacid ethyl ester). Compound 40(g) (3.20 g, 8.95 mmol) in DMF (120 mL)was added dropwise to a solution of N-chlorosuccinimide (1.19 g, 8.95mmol) and pyridine (catalytic) in DMF (60 mL). The reaction mixture waswarmed to 60° C. for 20 hours at which time an additional amount ofN-chlorosuccinimide (0.238 g, 1.79 mmol) was added to the reaction.After compound 40(b) was consumed (monitored by TLC), the reaction wascooled to ambient temperature. Triethylamine (1.26 mL, 8.95 mmol)followed by tetrahydro-2-(2-propynloxy)-2H-pyran (2.51 mL, 17.9 mmol)were added. The reaction was warmed to 60° C. for 2 hours, cooled toambient temperature, and extracted with ethyl acetate (2×100 mL). Thecombined organic layers were washed with ice cold water (several times)and brine, dried (MgSO₄) and concentrated in vacuo. Purification bycolumn chromatography (silica gel, ethyl acetate/hexanes gradient)provided 2.05 g (46%) of the desired product as a white solid.

i. Preparation of compound 40(i)(2-(4-fluoro-phenyl)-5-methoxy-6-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-benzofuran-3-carboxylicacid). Potassium Hydroxide solution (4N, 1.34 mL, 5.35 mmol) was addedto a suspension of compound 40(h) (1.06 g, 2.14 mmol) in ethanol (10mL). The reaction mixture was warmed to reflux for 2 hours, then cooledto room temperature. The reaction mixture was neutralized with 4MHCl_((aq)) (1.34 mL, 5.35 mmol), filtered, air dried, and dried undervacuum to provide 0.95 g (95%) of the desired product.

j. Preparation of compound 40(j)(2-(4-fluoro-phenyl)-5-methoxy-6-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-benzofuran-3-carboxylicacid methylamide). Carbonyldiimidazole (0.401 g, 2.47 mmol) was added toa suspension of compound 40(i) (0.958 g, 2.06 mmol) in dichloromethane.The resulting solution was stirred for 1 hour at ambient temperature.N-methyl amine (2.0M in THF, 1.55 mL, 3.09 mmol) was added, and thereaction was allowed to stir for 20 hours at ambient temperature. Themixture was then refluxed for 1 hour, cooled to ambient temperature andpartitioned between water and dichloromethane. The aqueous layer waswashed with ethyl acetate, and the combined organic layers were washedwith brine, dried (MgSO₄), filtered and concentrated in vacuo.Purification by column chromatography (silica gel, ethyl acetate/hexanesgradient) provided 0.46 g (46%) of the desired product.

k. Preparation of2-(4-fluoro-phenyl)-6-(5-hydroxymethyl-isoxazol-3-yl)-5-methoxy-benzofuran-3-carboxylicacid methylamide. Pyridinium p-toluenenesulfonate (7 mg, 0.028 mmol) wasadded to a solution of compound 40(e) (0.135 g, 0.281 mmol) in ethanol(10 mL), THF (3 mL), and water. The reaction mixture was stirred for 20hours at room temperature. The reaction mixture was then warmed to 95°C. for 4 hours, cooled to room temperature, and concentrated in vacuo.The residue was partitioned between ethyl acetate and water. The organiclayer was washed with brine, dried (MgSO₄) and concentrated in vacuo.Purification by column chromatography (silica gel, ethyl acetate/hexanesgradient) and crystallization from ethyl acetate provided 50 mg (45%) ofthe title compound.

Example 41 Preparation of2-(4-fluoro-phenyl)-6-[4-(2-hydroxy-ethyl)-isoxazol-3-yl]

a. Preparation of compound 41(a)(2-(4-fluoro-phenyl)-5-methoxy-6-(3a,4,5,6a-tetrahydro-furo[3,2-d]isoxazol-3-yl)-benzofuran-3-carboxylicacid ethyl ester). N-Chlorosuccinimide (0.747 g, 5.59 mmol) and pyridine(catalytic) were added to a solution of compound 40(g) (2.00 g 5.59mmol, which can be prepared according to Example 40, step g above), inDMF (100 mL). The reaction mixture was warmed to 60° C. for 20 hours.Triethylamine (0.78 mL, 5.59 mmol) followed by 2,3-dihydrofuran (0.85mL, 11.2 mmol) were added. The reaction was warmed to 60° C. for 1 hour,cooled to ambient temperature, diluted with water to 500 mL, andextracted with ethyl acetate (3×75 mL). The combined organic layers werewashed several times with ice cold water, once with brine, then dried(MgSO₄) and concentrated in vacuo to provide 2.27 g (95%) of the desiredproduct.

b. Preparation of compound 41(b)(2-(4-fluoro-phenyl)-5-methoxy-6-(3a,4,5,6a-tetrahydro-furo[3,2-d]isoxazol-3-yl)-benzofuran-3-carboxylicacid). Potassium hydroxide solution (4N, 0.73 mL, 2.93 mmol) was addedto a suspension of compound 41(a) (0.500 g, 1.17 mmol) in ethanol (7 mL)and water (2 mL). The reaction mixture was warmed to reflux for 1.5hours, then cooled to room temperature. The reaction mixture wasneutralized with 4M HCl_((aq)) (0.73 mL, 2.93 mmol), filtered, airdried, and dried under vacuum to provide 0.502 g (quantitative) of thedesired product, which was taken on to the next step without furtherpurification.

c. Preparation of compound 41(c)(2-(4-fluoro-phenyl)-5-methoxy-6-(3a,4,5,6a-tetrahydro-furo[3,2-d]isoxazol-3-yl)-benzofuran-3-carboxylicacid methylamide). Carbonyldiimidazole (0.20 g, 1.27 mmol) was added toa suspension of compound 41(b) (0.42 g, 1.05 mmol) in dichloromethane.The resulting solution was stirred for 2 hours at ambient temperature.N-methyl amine (2.0M in THF, 0.79 mL, 1.58 mmol) was added, and thereaction was refluxed for 3 hours, cooled to ambient temperature andpartitioned between water and ethyl acetate. The aqueous layer waswashed with ethyl acetate, then the combined organic layers were washedwith brine, dried (MgSO₄), filtered, and concentrated in vacuo. Theproduct was purified by column chromatography (silica gel, ethylacetate/hexanes gradient) to provide 0.30 g (70%) of the desiredcompound.

d. Preparation of2-(4-fluoro-phenyl)-6-[4-(2-hydroxy-ethyl)-isoxazol-3-yl]-5-methoxy-benzofuran-3-carboxylicacid methylamide. Compound 41(c) (0.160 g, 0.38 mmol) was suspended inethanol (15 mL) and concentrated HCl (3 drops). The reaction was warmedto reflux for 50 hours, cooled to ambient temperature, and partitionedbetween ethyl acetate and water. The layers were separated, and theorganic layer was washed with brine, dried (MgSO₄), filtered, andconcentrated in vacuo. Purification by column chromatography (silicagel, ethyl acetate/hexanes gradient) and crystallization from ethylacetate provided 50 mg (31%) of the title compound.

Example 42 Preparation of2-(4-fluoro-phenyl)-6-[(2-hydroxy-ethyl)-methanesulfonyl-amino]-5-methoxy-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 42(a)(2-(4-fluoro-phenyl)-5-hydroxy-6-nitro-benzofuran-3-carboxylic acidethyl ester). Boron trichloride (106 mL, 0.106 mol) was added todropwise to a solution of compound 21(d) (20.5 g, 0.053 mol, which canbe prepared according to Example 21, steps a-d, above) in anhydrousdichloromethane (264 mL), under argon. The reaction mixture was stirredat ambient temperature overnight. The reaction was quenched with icewater and extracted with dichloromethane (3×). The organic layers werecombined, dried over magnesium sulfate, filtered, and evaporated. Theresulting solid was sonicated in hexanes, filtered and dried to provide17.82 g (99%) of the product as a yellow solid.

b. Preparation of compound 42(b)(2-(4-fluoro-phenyl)-5-methoxy-6-nitro-benzofuran-3-carboxylic acidethyl ester). Cesium carbonate (33.04 g, 0.101 mol) and methyl iodide(31.6 mL, 0.507 mol) were added to a solution of compound 42(a) (17.5 g,0.053 mol) in 1-methyl-2-pyrrolidinone (250 mL). The reaction mixturewas heated to 50° C. overnight, quenched with water, extracted withethyl acetate (3×), and a portion of insoluble product was filtered. Theorganic layers were combined, dried (MgSO₄), and concentrated. Theresulting solid was combined with the previously isolated solid toprovide 14.91 g (82%) of the product as a yellow solid.

c. Preparation of compound 42(c)(6-amino-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acidethyl ester). 10% Palladium on carbon (0.900 g) was added to mixture ofcompound 42(b) (7.0 g, 0.0195 mol) in isopropyl acetate (32.0 mL). Thereaction mixture was shaken under 50 psig of hydrogen gas on a Parrshaker overnight. The reaction mixture was filtered through Celite™,rinsing with ethyl acetate and methanol. The filtrate was concentratedin vacuo. This reaction was repeated using the same quantities ofsolvents reactants, and the products of both reactions were combined toprovide a total of 12.8 g (99%) of the desired product as a solid.

d. Preparation of compound 42(d)(2-(4-fluoro-phenyl)-6-methanesulfonylamino-5-methoxy-benzofuran-3-carboxylicacid ethyl ester). Methanesulfonyl chloride (0.64 mL, 85.6 mmol) wasadded to a chilled solution (0° C., ice/water bath) of compound 42(c)(12.8 g, 12.8 mmol) in anhydrous dichloromethane (130 mL), under argon.The reaction mixture was then cooled using an ethanol/ice bath, andN,N-diisopropylethylamine (16.93 mL, 97.2 mmol) was added. The reactionmixture was stirred at ambient temperature overnight. The reactionmixture was diluted with water and extracted with dichloromethane (3×).The organic layers were combined, dried over magnesium sulfate, andevaporated to afford 18.7 g (99%) of the desired product as a solid.

e. Preparation of compound 42(e)(2-(4-fluoro-phenyl)-6-methanesulfonylamino-5-methoxy-benzofuran-3-carboxylicacid). Potassium hydroxide (51.5 g, 0.918 mol) was added to a mixture ofcompound 42(d) (18.7 g, 0.0459 mol) in ethanol (200 mL) and water (100mL) under argon. The reaction mixture was heated to reflux for about 7hours, then stirred at ambient temperature overnight. The reactionmixture was concentrated, and the residue was dissolved in water. Thewater mixture was acidified with 6N HCl until a solid precipitated. Thesolid was filtered, washed with water and dried to afford 15.0 g (86%)of the desired product as a tan solid.

f. Preparation of compound 42(f)(2-(4-fluoro-phenyl)-6-methanesulfonylamino-5-methoxy-benzofuran-3-carboxylicacid methylamide). 1,1-Carbonyldiimidizole (8.66 g, 53.3 mmol), followedby methylamine (2.0M in THF, 30.0 mL, 59.3 mmol) were added to asuspension of compound 42 (e) (15 g, 39.5 mmol) in dichloromethane (155mL) under argon. The reaction mixture was stirred at ambient temperatureovernight, diluted with water, extracted with dichloromethane (3×), anda portion of insoluble product was filtered and set aside. The organiclayers were combined, dried over magnesium sulfate, and evaporated. Theresulting solid was sonicated in water, filtered, and combined withpreviously isolated product to provide a total of 14.42 g (92%) of thedesired product.

g. Preparation of2-(4-fluoro-phenyl)-6-[(2-hydroxy-ethyl)-methanesulfonyl-amino-]-5-methoxy-benzofuran-3-carboxylicacid methylamide. Potassium iodide (80 mg, 0.48 mmol), potassiumcarbonate (2.82 g, 20.4 mmol), and 2-bromoethanol (3.62 mL, 51 mmol)were added to a solution of compound 42(f) (4.0 g, 10.2 mmol) dissolvedin anhydrous DMF (100 mL) under argon. The mixture was heated to 50° C.for 7 hours, and then additional amounts of potassium iodide (80 mg,0.48 mmol) and 2-bromoethanol (1.81 mL, 25.5 mmol) were added. Themixture was stirred at 50° C. overnight, and then an additional amountof potassium carbonate (19.73 g) was added. The reaction mixture wasstirred at 85° C. for about 4 hours, diluted with water, and extractedwith ethyl acetate (3×). The organic layers were combined andevaporated. The remaining solid was diluted with water, sonicated andfiltered. After several water washings, the solid was dried to afford3.14 g of crude product, which was subsequently crystallized from hotethanol.

Example 43 Preparation of5-cyclopropyl-2-(4-fluoro-phenyl)-6-[(2-hydroxy-ethyl)-methanesulfonyl-amino]-benzofuran-3-carboxylicacid methylamide

a. Preparation of cyclopropylboronic acid. Cyclopropylboronic acid wasprepared from cyclopropylmagnesium bromide, according to the literatureprocedure: Wallace, D. J., Chen, C., Tetrahedron Lett. 2002, 43,6987-6990, on a 4 g scale (56% yield).

b. Preparation of compound 43(b)(2-(4-fluoro-phenyl)-6-nitro-5-trifluoromethanesulfonyloxy-benzofuran-3-carboxylicacid ethyl ester). N,N-Diisopropylethylamine (8.8 mL, 56 mmol) and4-(dimethylamino)pyridine (0.618 g, 5.06 mmol) were added to asuspension of compound 42(a) (17.5 g, 50.6 mmol, which can be preparedaccording to Example 42, step a above), in anhydrous dichloromethane(300 mL) under argon. The reaction mixture was cooled to 0° C. in anice/water bath, and then trifluoromethanesulfonic anhydride (9.34 mL, 56mmol) was added. The reaction was stirred at ambient temperature forabout 5 hours, and then additional amounts of N,N-diisopropylethylamine(4.4 mL, 28 mmol) and trifluoromethanesulfonic anhydride (4.67 mL, 28mmol) were added. The reaction was stirred at room temperatureovernight, diluted with water and extracted with dichloromethane (3×).The organic layers were washed with water (3×) and 1N HCl (1×),combined, dried over magnesium sulfate, and evaporated. The residue wasrecrystallized from t-butylmethyl ether to provide a total of 20.36 g(84%) of the desired product as a yellow solid.

c. Preparation of compound 43(c)(5-cyclopropyl-2-(4-fluoro-phenyl)-6-nitro-benzofuran-3-carboxylic acidethyl ester). Anhydrous toluene (10.0 mL) was added to a mixture ofcyclopropylboronic acid (0.271 g, 3.14 mmol), potassium fluoridedihydrate (0.652 g, 6.92 mmol), sodium bromide (0.216 g, 2.16 mmol),tetrakis(triphenylphosphine)palladium(0) (0.073 g, 0.0629 mmol), andcompound 43(b) (1.0 g, 2.09 mmol). The resulting solution was degassedwith argon through a gas dispersion tube for 10 minutes. The reactionmixture was heated to reflux overnight, diluted with water, andextracted with ethyl acetate (3×). The organic layers were combined,dried over magnesium sulfate, and evaporated. The crude product waspurified by column chromatography (silica gel, dry loading, hexane/ethylacetate gradient) to afford 0.670 g (86%) of the desired product as asolid.

d. Preparation of compound 43(d)(6-amino-5-cyclopropyl-2-(4-fluoro-phenyl)-benzofuran-3-carboxylic acidethyl ester). 10% Palladium on carbon (0.150 g) and 1N HCl (7 drops)were added to a solution of compound 43(c) (0.665 g, 1.8 mmol) in ethylacetate (70.0 mL). The reaction mixture was shaken under 50 psig ofhydrogen gas on a Parr shaker overnight. The reaction mixture wasfiltered through Celite™, rinsing with ethyl acetate and methanol. Thefiltrate was concentrated in vacuo to afford 0.540 g (88%) of thedesired product as a solid.

e. Preparation of compound 43(e)(5-cyclopropyl-2-(4-fluoro-phenyl)-6-methanesulfonylamino-benzofuran-3-carboxylicacid). Methanesulfonylchloride (0.270 mL, 3.48 mmol) was added tochilled solution (0° C., ice/water bath) of compound 43(d) (0.535 g,1.58 mmol) dissolved in dichloromethane (6 mL). The reaction mixture wascooled further in an ethanol/ice bath, and thenN,N-diisopropylethylamine (0.688 mL, 3.95 mmol) was added. The reactionwas stirred at room temperature overnight, diluted with water, andextracted with dichloromethane (3×). The organic layers were combined,dried over magnesium sulfate, and evaporated to afford 0.653 g (86%) ofthe bis(sulfonylated) intermediate.

Potassium hydroxide (1.52 g, 27 mmol) was added to a solution of thebis(sulfonylated) intermediate (0.670 g, 1.35 mmol) dissolved in ethanol(10.0 mL) and water (5.0 mL) under argon. The reaction was heated toreflux overnight, and then concentrated in vacuo. The remaining solidwas dissolved in water, and the solution was acidified with 1N HCL untila precipitate formed. The solid was filtered and dried to afford 0.532 g(99%) of the desired product.

f. Preparation of compound 43(f)(5-cyclopropyl-2-(4-fluoro-phenyl)-6-methanesulfonylamino-benzofuran-3-carboxylicacid methylamide). Benzotriazol-1-yloxytrispyrrolidinophosphoniumhexafluorophosphate (PyBop) (1.02 g, 1.97 mmol) was added to a mixtureof methylamine (12.0 mL, 16.3 mmol, 2.0M in THF), DMF (1.0 mL), andcompound 43(e) (0.530 g, 1.36 mmol) under argon. The reaction wasstirred at room temperature overnight and then concentrated in vacuo.The residue was diluted with water and extracted with ethyl acetate(3×). The organic layers were combined, washed with water, dried overmagnesium sulfate, and air-dried to afford 0.347 g (63%) of crudeproduct. A portion of the crude product (100 mg) was purified by reversephase HPLC (acetonitrile/water gradient) to afford 0.050 g of thedesired product.

g. Preparation of compound 43(g)(6-[(2-benzyloxy-ethyl)-methanesulfonyl-amino]-5-cyclopropyl-2-(4-fluoro-phenyl)-benzofuran-3-carboxylicacid methylamide). Potassium carbonate (0.125 g, 0.91 mmol) and benzyl2-bromoethyl ether (0.105 mL, 0.67 mol) were added to a solution ofcompound 43(g) (0.120 g, 0.0003 mol), dissolved in acetonitrile (1.5 mL)under argon. The reaction mixture was heated to reflux overnight,diluted with water, and extracted with dichloromethane (3×). The organiclayers were combined, dried over magnesium sulfate, and evaporated. Thecrude product was purified by reprecipitating out of ethylacetate/hexanes, and the isolated solid was taken on to the next stepwithout further purification.

h. Preparation of(5-cyclopropyl-2-(4-fluoro-phenyl)-6-[(2-hydroxy-ethyl)-methanesulfonyl-amino]-benzofuran-3-carboxylicacid methylamide). 10% Palladium on carbon (0.100 g) was added tomixture of compound 43(g) (0.162 g, 0.41 mmol) in ethyl acetate (20 mL).The reaction mixture was shaken under 50 psig of hydrogen gas on a Parrshaker overnight. The reaction mixture was filtered through Celite™,rinsing with ethyl acetate and methanol. The filtrate was concentratedin vacuo, and the crude product was dissolved in ethyl acetate andprecipitated with hexanes. The solid was isolated by filtration toafford 0.083 g of desired product as a tan solid.

Example 44 Preparation of5-ethyl-2-(4-fluoro-phenyl)-6-methanesulfonylamino-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 44(a) (trifluoro-methanesulfonic acid2-(4-fluoro-phenyl)-6-methanesulfonylamino-3-methylcarbamoyl-benzofuran-5-ylester). A solution of N-phenyltriflimide (14.2 g, 39.68 mmol) inanhydrous dichloromethane (20 mL) followed by triethylamine (5.4 mL,52.9 mmol) were introduced to a suspension of compound 38(a) (10 g,26.45 mmol, which can be prepared according to Example 38 step a above),in anhydrous dichloromethane (110 mL) at 0° C. under argon. The reactionmixture was stirred at room temperature overnight. The reaction mixturewas poured into water (150 mL), and the layers were separated. Theaqueous layer was extracted with dichloromethane (3×100 mL). Thecombined organic layers were dried (MgSO₄) and concentrated undervacuum. The crude product was purified by recrystallization (1:1 ethylacetate/hexanes) to provide 12.7 g (94%) of the desired product as lightorange crystals.

b. Preparation of compound 44(b)(2-(4-fluoro-phenyl)-6-methanesulfonylamino-5-vinyl-benzofuran-3-carboxylicacid methylamide). Lithium chloride (498 mg, 11.75 mmol),tetrakis-triphenylphosphinepalladium(0) (90 mg, 0.08 mmol),triphenylphosphine (83 mg, 0.31 mmol) and2,6-di-tert-butyl-4-methylphenol (about 16 mg, 0.08 mmol) were added toa solution of compound 44(a) (2.0 g, 3.92 mmol) in anhydrous 1,4-dioxane(17.6 mL) under argon. The reaction was degassed with argon for 15minutes. Tri-n-butylethenyl-stannane (1.17 mL) was introduced viasyringe, and the reaction was then heated to 100° C. for 18 hours. Thereaction mixture was poured into a saturated aqueous solution ofpotassium fluoride (50 mL) and vigorously stirred for 4 hours. Thelayers were separated, and the aqueous layer was extracted withdichloromethane (3×50 mL). The combined organic layers were washed with10% ammonium hydroxide solution (3×50 mL). The latter aqueous layerswere extracted with of dichloromethane (50 mL). All organic layers werecombined, dried (MgSO₄), and concentrated. The residue was purified byflash chromatography (silica gel, hexane, then dichloromethane/hexanesgradient) and recrystallization (ethyl acetate) to provide 1.10 g (72%)of the desired product.

c. Preparation of5-ethyl-2-(4-fluoro-phenyl)-6-methanesulfonylamino-benzofuran-3-carboxylicacid methylamide. 10% Palladium on carbon (50 mg) was added to mixtureof compound 44(b) (500 mg, 1.29 mmol) in ethyl acetate (50 mL). Thereaction mixture was shaken under 50 psig of hydrogen gas on a Parrshaker for 2 days. The reaction mixture was filtered through Celite™,rinsing with ethyl acetate and ethanol, and the product was purified byHPLC (reverse phase, acetonitrile/water gradient with 0.1% of aceticacid) affording 342 mg (74%) of desired product.

Example 45 Preparation of5-ethyl-2-(4-fluoro-phenyl)-6-(methanesulfonyl-methyl-amino)-benzofuran-3-carboxylicacid methylamide

The title compound was prepared essentially according to the generalprocedure described in Example 38, step b above; however,5-ethyl-2-(4-fluoro-phenyl)-6-methanesulfonylamino-benzofuran-3-carboxylicacid methylamide (which can be prepared according Example 44) was usedinstead of compound 38(a). The crude product was purified via HPLC toprovide the product in a 64% yield.

Example 46 Preparation of5-ethyl-2-(4-fluoro-phenyl)-6-[(2-hydroxy-ethyl)-methanesulfonyl-amino]-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 46(a)(6-[(2-benzyloxy-ethyl)-methanesulfonyl-amino]-2-(4-fluoro-phenyl)-5-vinyl-benzofuran-3-carboxylicacid methylamide). Benzyl-2-bromoethyl ether (448 uL, 2.82 mmol) wasadded to a suspension of compound 44(b) (500 mg, 1.28 mmol), which canbe prepared according to Example 44 steps a-b above, and potassiumcarbonate (534 mg, 3.86 mmol) in anhydrous acetonitrile (6.4 mL), underargon. The mixture was heated to reflux for 12 hours, poured over water(100 mL), and extracted with dichloromethane (3×100 mL). The organiclayers were combined, washed with brine (100 mL), dried over MgSO₄, andconcentrated. The crude product was purified via flash chromatography(silica gel, dichloromethane/methanol gradient) to afford 650 mg (97%)of the desired product.

b. Preparation of5-ethyl-2-(4-fluoro-phenyl)-6-[(2-hydroxy-ethyl)-methanesulfonyl-amino]-benzofuran-3-carboxylicacid methylamide. 10% Palladium on carbon (3 additions of 50 mg/day, 150mg total) was added to mixture of compound 46(a) (650 mg, 1.28 mmol) inethyl acetate (65 mL). The reaction mixture was shaken under 50 psig ofhydrogen gas on a Parr shaker for 4 days. The reaction mixture wasfiltered through Celite™, rinsing with ethyl acetate. The filtrate wasconcentrated in vacuo, and a solid was isolated. The crude product waspurified by HPLC (reverse phase, acetonitrile/water gradient with 0.1%of acetic acid), to afford 398 mg (78%) of the titled compound.

Example 47 Preparation of6-(1-acetyl-pyrrolidin-2-yl)-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 47(a)(6-bromo-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acidmethylamide). The intermediate compound was prepared essentiallyaccording to the general procedure described in Example 28, step gabove; however, compound 28(c) was used instead of compound 28(f).

b. Preparation of compound 47(b)(2-[2-(4-fluoro-phenyl)-5-methoxy-3-methylcarbamoyl-benzofuran-6-yl]-pyrrole-1-carboxylicacid tert-butyl ester). To a mixture of compound 47(a) (527 mg, 1.40mmol, which can be prepared according to the general proceduresdescribed in the previous step), 1-(t-butoxycarbonyl)pyrrole-2-boronicacid (445 mg, 2.10 mmol) in a degassed solvent of toluene/ethanol/water(20 mL/10 mL/0.5 mL) was added solid Na₂CO₃ (371 mg, 3.5 mmol) andtetrakis-triphenylphosphine-palladium(0) (81 mg, 0.07 mmol) at roomtemperature. After stirring for 20 hours at 85° C. under argonatmosphere, the reaction was quenched with water and extracted withethyl acetate. The organic phase was washed with water and brine, driedover MgSO₄, and concentrated under reduced pressure. The crude productwas purified by column chromatography (silica gel, 20% ethyl acetate inhexanes) to yield desired product 550 mg (85%) as a light yellow solid.

c. Preparation of compound 47(c)(2-[2-(4-fluoro-phenyl)-5-methoxy-3-methylcarbamoyl-benzofuran-6-yl]-pyrrolidine-1-carboxylicacid tert-butyl ester). To a solution of compound 47(b) (500 mg, 1.08mmol) in 4:1 ethyl acetate:ethanol was added activated 10% palladium oncarbon (200 mg, 10% weight). The mixture was allowed to stir under 50psig of hydrogen gas on a Parr-shaker overnight at room temperature.Another portion of activated 10% palladium on carbon (200 mg, 10%weight) was added. The mixture was agitated for another 24 hours under50 psig of hydrogen gas on a Parr-shaker at room temperature. Thereaction was then filtered through a pad of Celite™, rinsing with ethylacetate. Concentration of the filtrate gave 480 mg (95%) of pureexpected compound as a white solid.

d. Preparation of compound 47(d)(2-(4-fluoro-phenyl)-5-methoxy-6-pyrrolidine-2-yl-benzofuran-3-carboxylicacid methylamide). Compound 47(c) (450 mg, 0.96 mmol) in a solution of20% (vol.) trifluoroacetic acid in dichloromethane was stirred at roomtemperature for one hour. The solvent was then removed under reducedpressure, and the residue was dissolved in dichloromethane and treatedwith excess triethylamine for 30 minutes. The solvent was in vacuo, andthe residue was used in the next step without further purification.

e. Preparation of compound6-(1-acetyl-pyrrolidin-2-yl)-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylicacid methylamide. Acetic anhydride (18 μL, 0.186 mmol) was addeddropwise to a solution of compound 47(c) (45 mg, 0.124 mmol) indichloromethane at 0° C. The resulting mixture was stirred at 0° C. toroom temperature for 24 hours. The reaction was quenched with water andextracted into ethyl ether. The organic layer was washed with NaHCO₃ andbrine, dried over Na₂SO₄, and evaporated under reduced pressure. Thecrude material was purified by column chromatography (silica gel, 10%methanol in ethyl acetate) to provide 40 mg (80%) of the desired productas a white solid.

Example 48 Preparation of2-(4-fluoro-phenyl)-5-methoxy-6-(2-oxo-oxazolidin-5-yl)-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 48(a)(2-(4-fluoro-phenyl)-6-formyl-5-methoxy-benzofuran-3-carboxylic acidmethylamide). TiCl₄ (276 μL, 3.0 mmol) was slowly added to a solution ofa,a-dichloromethyl methylether (107 μL, 1.20 mmol) in dichloromethane (1mL) at 0° C., followed by addition of a suspension of compound 47(a)(300 mg, 1 mmol, which can be prepared according to Example 47, step aabove) in dichloromethane (6 mL). After the addition was complete, theice-bath was removed. The mixture was stirred for 1.5 hours at roomtemperature, then poured into ice water and extracted with ethylacetate. The organic phase was washed with water and brine, dried overMgSO₄, and concentrated under reduced pressure. The crude product waspurified by column chromatography (silica gel, 30-50% ethyl acetate inhexanes) to yield the desired product 196 mg (60%) as a white solid.

b. Preparation of compound 48(b)(6-(cyano-trimethylsilanyloxy-methyl)-2-[2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylicacid methylamide). To a mixture of compound 48(a) (80 mg, 0.25 mmol) andtrimethylsilyl cyanide (40 μL, 0.3 mmol) in dichloromethane (1 mL) at 0°C. was added ZnI₂ (catalytic amount). After stirred for 30 minutes at 0°C., another portion of trimethylsilyl cyanide (30 μL) was added. Theresulting mixture was stirred for one hour at 0° C. and two hours atroom temperature. The reaction was quenched with water and extractedwith dichloromethane. The organic phase was washed with water and brine,dried over MgSO₄, and concentrated under reduced pressure. The crudeproduct (90 mg) was taken on to the next step without furtherpurification.

c. Preparation of compound 48(c)(6-(2-amino-1-hydroxy-ethyl)-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylicacid methylamide). To a solution of compound 48(c) (90 mg in 10:1ethanol/acetic acid) was added activated 10% palladium on carbon (20mg). The mixture was allowed to stir under 50 psig of hydrogen gas on aParr-shaker for 48 hours at room temperature. The reaction mixture wasfiltered through a pad of Celite™, rinsing with ethyl acetate.Concentration of the filtrate under reduced pressure provided 60 mg ofthe product (90% purity by LC/MS).

d. Preparation of2-(4-fluoro-phenyl)-5-methoxy-6-(2-oxo-oxazolidin-5-yl)-benzofuran-3-carboxylicacid methylamide. To a mixture of compound 48(c) (60 mg, 0.15 mmol, 90%purity) and triethylamine (63 μL, 0.45 mmol) in dichloromethane (1 mL)was added phosgene (12 μL, 20% solution in toluene) at 0° C. Theresulting mixture was stirred for one hour at 0° C. and for one hour atroom temperature. The solvent was removed under reduced pressure. Theresidue was purified by HPLC (reverse phase) to provide 35 mg (67%) ofthe title compound as a white solid.

Example 49 Preparation of2-(4-fluoro-phenyl)-6-(1-hydroxy-1-methyl-ethyl)-5-methoxy-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 49(a)(6-acetyl-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acidmethylamide). A sealed tube was charged with magnetic stirrer, compound24(b) (1.22 g, 3.0 mmol, which can be prepared according to Example 24,step b above), palladium(II) acetate (34 mg, 0.015 mmol),[1,1′-bis(diphenylphosphino)propane] (DPPP) (136 mg, 0.33 mmol), butylvinyl ether (1.92 mL, 15 mmol), and K₂CO₃ (622 mg, 4.5 mmol) in DMF (5mL). The tube was flushed with argon, sealed, and heated to 100° C. for24 hours, then cooled to room temperature. 5% HCl (20 mL) was addeddropwise over 20 minutes, and the mixture with extracted with ethylacetate. The organic layer was washed with water and brine, dried overMgSO₄, and concentrated under reduced pressure. The crude material waspurified by column chromatography (silica gel, 20% ethyl acetate inhexanes) to yield 0.94 g (85%) of the desired product.

b. Preparation of compound 49(b)(6-acetyl-2-(4-fluoro-phenyl)-5-hydroxy-benzofuran-3-carboxylic acidmethylamide). Boron trichloride (27.1 mL, 1.0M in dichloromethane) wasslowly added to a solution of compound 49(a) (5.0 g, 13.6 mmol) indichloromethane (58 mL) at 0° C. under argon. The mixture was stirred at0° C. to room temperature for 1 hour. The mixture was poured into icewater (250 mL) and extracted with ethyl acetate. The organic layer waswashed with saturated NaHCO₃ and brine, dried over MgSO₄, andconcentrated under reduced pressure. The crude material was purified bycolumn chromatography (silica gel, 30% ethyl acetate in hexanes) toyield 3.85 g (87%) of the desired product.

c. Preparation of compound 49(c)(6-acetyl-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acidmethylamide). To a mixture of compound 49(b) (1.35 g, 4.1 mmol) andcesium carbonate (2.7 g, 8.3 mmol) in NMP (2 mL) was added methyl iodide(0.65 mL, 10.2 mmol). The resulting mixture was stirred at roomtemperature for 24 hours. The reaction was quenched with water (50 mL)and extracted with ethyl acetate. The organic layer was washed withwater and brine, dried over MgSO₄, and concentrated under reducedpressure. The crude product was purified by column chromatography(silica gel, 35% ethyl acetate in hexanes) to yield 1.17 g (83%) of thedesired product.

d. Preparation of2-(4-fluoro-phenyl)-6-(1-hydroxy-1-methyl-ethyl)-5-methoxy-benzofuran-3-carboxylicacid methylamide. To a stirred solution of methylmagnesium bromide (1.4Min toluene/THF, 2.6 mL, 3.6 mmol) at 0° C. was added compound 49(c) (500mg, 1.5 mmol) in THF (1 mL). The resulting mixture was stirred at 0° C.to room temperature for 1 hour. The reaction was quenched with saturatedNH₄Cl (1 mL) and extracted with ethyl acetate. The organic layer waswashed with water and brine, dried over MgSO₄, and concentrated underreduced pressure. The crude material was purified by columnchromatography (silica gel, 50% ethyl acetate in hexanes) to provide 361mg (70%) of the desired product.

Example 50 Preparation of2-(4-fluoro-phenyl)-5-methoxy-6-(5-methyl-[1,2,4]oxadiazol-3-yl)-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 50(a)(6-cyano-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylic acidmethyl ester). Anhydrous 1-methyl-2-pyrrolidinone (60 mL) was added to amixture of compound 28(d) (2.2 g, 5.80 mmol, which can be preparedaccording to Example 28, steps a-d, above) and copper(I) cyanide (1.04g, 11.61 mmol) and heated to 170° C. After stirring for 16 hours underargon, the reaction mixture was cooled to room temperature. Water (200mL) and ethyl acetate (300 mL) were added, and the solution was filteredthough Celite™, rinsing with ethyl acetate. The organic layer wasseparated and washed with water (3×100 mL) and brine, dried over MgSO₄,and concentrated under reduced pressure. The crude product was purifiedby column chromatography (silica gel 20-40% ethyl acetate in hexanes) toyield 1.5 g (79%) of the desired product.

b. Preparation of compound 50(b)(2-(4-fluoro-phenyl)-6-(N-hydroxycarbamimidoyl)-5-methoxy-benzofuran-3-carboxylicacid methyl ester). To a stirred suspension of compound 50(a) (340 mg,1.046 mmol) in ethanol (5.0 mL) and triethylamine (393 μL, 2.824 mmol)was added hydroxylamine hydrochloride (182 mg, 2.62 mmol). The reactionmixture was stirred at 75° C. for 12 hours, cooled to room temperature,diluted with water (100 mL) and filtered. The isolated solid was washedwith water and hexanes and dried in a vacuum oven to yield 300 mg (80%)of the desired compound.

c. Preparation of compound 50(c)(2-(4-fluoro-phenyl)-5-methoxy-6-(5-methyl-[1,2,4]oxadiazol-3-yl)-benzofuran-3-carboxylicacid methyl ester). Pyridine (65 mg, 3.3519 mmol) followed by aceticanhydride (237 μL, 2.55 mmol) were added to a solution of compound 50(b)(300 mg, 0.838 mmol) dissolved in 1,2-dichloroethane (10 mL). Afterrefluxing for 12 hours under argon, the reaction mixture was cooled toroom temperature, diluted with water, and extracted withdichloromethane. The organic layer was washed with water and brine,dried over MgSO₄, and concentrated. The crude product was purified bycolumn chromatography (silica gel, 10-30% ethyl acetate in hexanes) toprovide 80 mg (50%) of the desired product.

d. Preparation of2-(4-fluoro-phenyl)-5-methoxy-6-(5-methyl-[1,2,4]oxadiazol-3-yl)-benzofuran-3-carboxylicacid methylamide. The title compound (55 mg) was prepared essentiallyaccording to the general procedures described in Example 15, steps b andc, above; however in step b compound 50(c) was used instead of compound15(a).

Example 51 Preparation of6-(3,5-dimethyl-isoxazol-4-yl)-2-(4-fluoro-phenyl)-5-(3-hydroxy-propoxy)-benzofuran-3-carboxylicacid methylamide

a. Preparation of compound 51(a)(6-(3,5-dimethyl-isoxazol-4-yl)-2-(4-fluoro-phenyl)-5-hydroxy-benzofuran-3-carboxylicacid methylamide). The intermediate compound 51(a) was preparedessentially according to the general procedure described in Example 29,step a above; however,6-(3,5-dimethyl-isoxazol-4-yl)-2-(4-fluoro-phenyl)-5-methoxy-benzofuran-3-carboxylicacid methylamide (which can be prepared according to Example 28, above)was used instead of2-(4-fluoro-phenyl)-5-isopropoxy-6-methanesulfonylamino-benzofuran-3-carboxylicacid methylamide.

b. Preparation of6-(3,5-dimethyl-isoxazol-4-yl)-2-(4-fluoro-phenyl)-5-(3-hydroxy-propoxy)-benzofuran-3-carboxylicacid methylamide. Compound 51(a) (0.250 g, 0.657 mmol),3-bromo-1-propanol (0.12 mL, 1.33 mmol), potassium carbonate (0.227 g,1.64 mmol) and potassium iodide (0.011 g, 0.066 mmol) were combined withanhydrous acetonitrile (4 mL) in an oven-dried flask under argon. Thereaction was refluxed with stirring for 4 hours, cooled to roomtemperature, and diluted with water (5 mL). The resulting precipitatewas filtered, washed with water and hexanes, and dried to provide 0.241g (84%) of the title compound as a white solid.

By appropriate selection of suitable starting materials, other compoundsof the invention may be prepared according to the procedures describedin the foregoing examples. Representative examples of further benzofuranderivatives and analogues thus prepared are set forth in Table 1 below.

TABLE 1 HCV pol-BB7 IC₅₀ (μM) A = ≦0.5 μM Ex- B = 0.5 to ≦5.0 μM ampleMass C = 5.0 to ≦30 μM Replicon Number Name NMR data* Spec D = >30 μM(μM) 1. 2-Furan-3-yl-5-methoxy- *** (M + H)⁺ = 272 B <30benzofuran-3-carboxylic acid methylamide 2. 2-Phenyl-5- ¹H NMR inDimethyl-d₆ (M + H)⁺ = 336 B *** trifluoromethoxy- Sulfoxide (DMSO):benzofuran-3-carboxylic 8.47-8.49 (d, J = 4.69 Hz, H); acid methylamide7.88-7.91 (dd, J = 1.76 Hz, 8.21 Hz, 2H); 7.80-7.83 (d, J = 9.38 Hz,1H); 7.50-7.57 (m, 3H); 7.38-7.41 (d, J = 8.79 Hz, 1H); 2.83-2.84 (d, J= 4.69 Hz, 3H) 3. 2-(3,4-Difluoro-phenyl)- ¹H NMR in DMSO: (M + H)⁺ =318 A <10 5-methoxy-benzofuran-3- 8.44 (s, 1H); 7.98 (m, 1H); carboxylicacid 7.74 (m, 1H); 7.60 (m, 2H); 7.12 (m, methylamide 1H); 7.03 (m, 1H);3.82 (s, 3H); 2.85 (d, J = 4.2 Hz, 3H) 4. 2-[4-(Acetylamino- ¹H NMR inDMSO: (M + H)⁺ = 381 B <30 methyl)-phenyl]-5- 8.35 (brm, 2H); 7.78 (d,2H, isopropoxy-benzofuran- J = 8.21); 7.52 (d, 1H, J = 8.79);3-carboxylic acid 7.36 (d, 2H, J = 7.03); 7.04 (d, methylamide 1H, J =2.34); 6.93 (dd, 1H, J = 8.79, 2.34); 4.59 (m, 1H); 4.28 (d, 2H, J =5.86); 2.80 (d, 3H, J = 4.69); 1.87 (s, 3H); 1.26 (d, 6H, J = 5.86) 5.2-(4-Hydroxy-phenyl)-5- ¹H NMR in DMSO: (M − H)⁻ = 324 B <10isopropoxy-benzofuran- 9.91 (s, 1H); 8.20 (d, 1H, 3-carboxylic acid J =4.69); 7.70 (d, 2H, J = 8.79); methylamide 7.47 (d, 1H, J = 8.79); 7.02(d, 1H, J = 2.34); 6.86 (m, 3H); 4.57 (m, 1H); 2.79 (d, 3H, J = 4.69);1.26 (d, 6H, J = 5.86) 6. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M +H)⁺ = 397 A <1 isopropoxy-6-pyrrolidin- 8.26 (d, J = 4.84, 1H);1-yl-benzofuran-3- 7.89-7.84 (m, 2H); 7.31 (t, J = 8.79, 2H); carboxylicacid 6.98 (s, 1H); 6.90 (s, 1H); methylamide 4.56 (septet, J = 6.15,1H); 3.33-3.29 (m, 4H); 2.81 (d, J = 4.40, 3H); 1.90-1.86 (m, 4H); 1.29(d, J = 6.15, 6H) 7. 5-Difluoromethoxy-2-(4- ¹H NMR inTrichloromethane-d (M + H)⁺ = 336 B <10 fluoro-phenyl)- (CDCl₃):benzofuran-3-carboxylic 7.92 (m, 2H); 7.61 (d, 1H, acid methylamide J =2.93); 7.48 (d, 1H, J = 8.79); 7.22-7.13 (m, 3H); 6.54 (t, 1H, J = 74);5.80 (brs, 1H); 3.00 (d, 3H, J = 5.27) 8. 2-(4-Fluoro-phenyl)-5- ¹H NMRin DMSO: (M + H)⁺ = 401 A <1 isopropoxy-6-(2- 8.25 (d, J = 4.69, 1H);methoxy-ethylamino)- 7.88-7.83 (m, 2H); 7.31 (t, J = 8.79, 2H);benzofuran-3-carboxylic 6.97 (s, 1H); 6.83 (s, 1H); acid methylamide5.04 (t, J = 5.27, 1H); 4.62-4.50 (septet, J = 5.27, 1H); 3.56 (t, J =5.27, 2H); 3.33-3.30 (m, 5H); 2.82 (d, J = 4.69, 3H); 1.31 (d, J = 5.86,6H) 9. 5-Methyl-2-phenyl- ¹H NMR in CDCl₃: (M + H)⁺ = 266 B <10benzofuran-3-carboxylic 7.91-7.86 (m, 2H); 7.66 (s, 1H); acidmethylamide 7.52-7.37 (m, 4H); 7.14 (d, J = 8.8 Hz, 1H); 5.81 (brs, 1H);2.97 (d, J = 4.7 Hz, 3H); 2.46 (s, 3H) 10. 5-Methyl-2-(4-fluoro- ¹H NMRin CDCl₃: (M + H)⁺ = 284 B <10 phenyl)benzofuran-3- 7.97-7.93 (m, 2H);7.59 (s, 1H); carboxylic acid 7.39 (d, J = 8.2 Hz, 1H); methylamide7.19-7.14 (m, 3H); 5.81 (br s, 1H); 3.02 (d, J = 5.3 Hz, 3H); 2.47 (s,3H) 11. 2-Phenyl-5-(2,2,2- ¹H NMR in CDCl₃: (M + H)⁺ = 350 D <30trifluoro-ethoxy)- 7.87 (dd, 2H); 7.65 (dd, 1H); benzofuran-3-carboxylic7.47-7.54 (m, 4H); 7.08 (dd, acid methylamide 1H); 5.8 (s, br, 1H); 3.93(s, 2H); 2.97 (d, 3H) 12. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M +H)⁺ = 299.9 A <10 methoxy-benzofuran-3- 8.37 (br.s, 1H); 7.91-7.96 (m,carboxylic acid 2H); 7.56-7.58 (d, J = 8.79 Hz methylamide 1H);7.34-7.40 (t, J = 8.79 Hz, 2H); 7.09-7.10 (d, J = 2.35 Hz, 1H);6.97-7.00 (dd, J = 2.35 Hz, 8.79 Hz, 1H); 3.82 (s, 3H); 2.83-2.8 (d, J =4.69 Hz, 3H) 13. 6-Bromo-2-(4-fluoro- ¹H NMR in DMSO: *** A <1phenyl)-5-methoxy- 8.42 (d, J = 4.69 Hz, 1H); 8.01 (s,benzofuran-3-carboxylic 1H); 7.90-7.94 (m, 2H); acid methylamide7.35-7.41 (t, J = 8.79 Hz, 2H); 7.23 (s, 1H); 3.91 (s, 3H); 2.83-2.85(d, J = 4.69 Hz, 3H) 14. 5-Methoxy-6-methyl-2- ¹H NMR in DMSO: (M + H)⁺= 296 A <1 phenyl-benzofuran-3- 8.34-8.36 (d, J = 4.69 Hz, 1H);carboxylic acid 7.83-7.86 (dd, J = 1.76 Hz, methylamide 8.79 Hz, 2H);7.43-7.53 (m, 4H); 7.04 (s, 1H); 3.85 (s, 3H); 2.83-2.84 (d, J = 4.69Hz, 3H); 2.28 (s, 3H) 15. 6-(3-Amino-pyrrolidin-1- *** (M + H)⁺ = 412 C<30 yl)-2-(4-fluoro-phenyl)- 5-isopropoxy-2,3- dihydro-benzofuran-3-carboxylic acid methylamide 16. 6-Amino-2-(4-fluoro- ¹H NMR in CDCl₃:(M + H)⁺ = 343 A <10 phenyl)-5-isopropoxy- 7.82 (dd, 2H, J = 5.5 and 8.7Hz); benzofuran-3-carboxylic 7.22 (s, 1H); 7.18 (t, 2H, acid methylamideJ = 8.7 Hz); 6.84 (s, 1H); 5.76 (brs, 1H); 4.61 (heptuplet, J = 6.1 Hz);2.96 (d, J = 4.9 Hz, 3H); 1.92 (brs, 2H); 1.40 (d, J = 6.1 Hz, 6H) 17.6-Amino-2-(4-fluoro- ¹H NMR in methanol-d₄ (M + H)⁺ = 315 B <10phenyl)-5-methoxy- (CD₃OD): benzofuran-3-carboxylic 7.81 (m, 2H); 7.20(m, 2H); acid methylamide 7.02 (s, 1H); 6.91 (s, 1H); 4.72 (s, 1H); 3.91(s, 3H); 2.93 (s, 3H) 18. 6-Acetylamino-2-(4- ¹H NMR in CDCl₃: (M + H)⁺= 357 A <1 fluoro-phenyl)-5- 7.95 (brs, 1H); 7.83 (m, 2H);methoxy-benzofuran-3- 7.46 (m, 1H); 7.38 (s, 1H); carboxylic acid 7.28(m, 2H); 5.76 (brs, 1H); 3.96 (s, methylamide 3H); 2.98 (s, 3H); 2.21(s, 3H) 19. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 357 A <1isopropoxy-6- 7.81 (dd, J = 8.7 & 5.1 Hz, 2H); methylamino- 7.25 (s,1H); 7.14 (t, J = 9.3 Hz, benzofuran-3-carboxylic 2H); 6.66 (s, 1H);5.78 (brs, acid methylamide 1H); 4.63 (septuplet, J = 6.3 Hz, 1H); 4.55(brs, 1H); 2.97 (d, J = 4.8 Hz, 3H); 2.91 (s, 3H); 1.37 (d, J = 6.3 Hz,6H) 20. 6-Dimethylamino-2-(4- ¹H NMR in CDCl₃: (M + H)⁺ = 371 A <1fluoro-phenyl)-5- 7.51 (dd, J = 8.7 & 5.1 Hz, 2H);isopropoxy-benzofuran- 7.28 (s, 1H); 7.26 (m, 3H); 3-carboxylic acid5.80 (brs, 1H); 4.70 (septuplet, methylamide J = 6.3 Hz, 1H); 2.98 (d, J= 4.9 Hz, 3H); 2.91 (s, 6H); 1.42 (d, J = 6.3 Hz, 6H) 21.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 421 A <1isopropoxy-6- 7.81 (dd, J = 8.7 & 4.1 Hz, 2H); methanesulfonylamino-7.73 (s, 1H); 7.42 (s, 1H); benzofuran-3-carboxylic 7.19 (t, J = 8.7 Hz,2H); 6.90 (s, 1H); acid methylamide 5.81 (brs, 1H); 4.75 (septuplet, J =6.3 Hz, 1H); 2.98 (s, 3H); 2.95 (d, J = 2.6 Hz, 3H); 1.40 (d, J = 6.3Hz, 6H) 22. 6-Ethylamino-2-(4- ¹H NMR in CDCl₃: (M + H)⁺ = 371 A <1fluoro-phenyl)-5- 7.81 (dd, J = 8.8, 5.3 Hz, 2H); isopropoxy-benzofuran-7.18 (s, 1H); 7.16 (t, J = 8.8 Hz, 3-carboxylic acid 2H); 6.67 (s, 1H);5.76 (brs, methylamide 1H); 4.61 (heptuplet, J = 6.2 Hz, 1H,); 3.20(quadruplet, J = 7.0 Hz, 2H); 2.97 (d, J = 4.8 Hz, 3H); 1.38 (d, J = 6.2Hz, 6H); 1.32 (t, J = 7.0 Hz, 3H) 23. 6-Diethylamino-2-(4- ¹H NMR inCDCl₃: (M + H)⁺ = 399 A <1 fluoro-phenyl)-5- 7.83 (dd, J = 8.8, 5.3 Hz,2H); isopropoxy-benzofuran- 7.26 (s, 1H); 7.15 (d, J = 8.8 Hz,3-carboxylic acid 2H); 7.05 (s, 1H); 5.78 (brs, 1H,; methylamide 4.17(heptuplet, J = 6.1 Hz, 1H); 3.18 (m, 4H); 2.95 (d, 5.0 Hz, 3H); 1.38(d, J = 6.1 Hz, 6H); 1.32 (t, J = 7.0 Hz, 6H) 24. 2-(4-Fluoro-phenyl)-5-¹H NMR in DMSO: (M + H)⁺ = 413 A <1 isopropoxy-6-morpholin- 8.30-8.31(d, J = 4.69 Hz, 1H); 4-yl-benzofuran-3- 7.88-7.93 (m, 2H); 7.31-7.37(t, carboxylic acid J = 8.79 Hz, 2H); 7.19 (s, 1H); methylamide 7.07 (s,1H); 4.58-4.66 (septet, J = 6.45 Hz, 1H); 3.75-3.77 (m, 4H); 3.02-3.05(m, 4H); 2.82-2.83 (d, J = 4.69 Hz, 3H); 1.29-1.31 (d, J = 6.45 Hz, 6H)25. 5-Methoxy-4-methyl-2- ¹H NMR in CDCl₃: (M + H)⁺ = 296 D >30phenyl-benzofuran-3- 7.84-7.81 (m, 2H); carboxylic acid 7.48-7.40 (m,3H); 7.30-7.26 (m, 1H); methylamide 6.93 (d, J = 8.7 Hz, 1H); 3.86 (s,3H); 3.01 (d, J = 4.8 Hz, 3H); 2.40 (s, 3H) 26. 5-Cyano-2-phenyl- ¹H NMRin CDCl₃: (M − H)⁻ = 275 C <30 benzofuran-3-carboxylic 8.32 (s, 1H);7.89-7.85 (m, 2H); acid methylamide 7.62-7.47 (m, 5H); 5.80 (s, 1H);2.98 (d, J = 5.1 Hz, 3H); 27. 5-Isopropoxy-2-pyridin- ¹H NMR in CDCl₃:(M + H)⁺ = 311 C >30 4-yl-benzofuran-3- 8.70 (d, J = 5.4 Hz, 2H); 7.84(dd, carboxylic acid J = 1.2 Hz, 4.2 HZ, 2H); 7.43 (d, methylamide J =8.7 Hz, 1H); 7.21 (d, J = 2.7 Hz, 1H); 7.00 (dd, J = 2.1 Hz, 8.7 Hz,1H); 5.91 (brs, 1H); 4.54 (m, 1H); 3.07 (d, J = 5.1 Hz, 3H); 1.36 (d, J= 5.7 Hz, 3H) 28. 6-(3,5-Dimethyl- ¹H NMR in CDCl₃: (M + H)⁺ = 395 A <1isoxazol-4-yl)-2-(4- 7.85-7.89 (m, 2H); 7.43 (s, 1H); fluoro-phenyl)-5-7.25 (s, 1H); 7.18-7.23 (t, J = 8.79 Hz, methoxy-benzofuran-3- 2H); 5.79(brs, 1H); 3.86 (s, carboxylic acid 3H); 3.00-3.02 (d, J = 5.28 Hz,methylamide 3H); 2.32 (s, 3H); 2.18 (s, 3H) 29. 2-(4-Fluoro-phenyl)-6-¹H NMR in CDCl₃: (M + H)⁺ = 407 A <1 (methanesulfonyl- 7.86 (m, 2H);7.56 (s, 1H); methyl-amino)-5- 7.45 (s, 1H); 7.28 (t, 8.3 Hz, 2H);methoxy-benzofuran-3- 5.77 (brs, 1H); 3.98 (s, 3H); 3.33 (s, carboxylicacid 3H); 2.98 (d, J = 5.2 Hz, 3H); methylamide 2.96 (s, 3H) 30.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 491 A <1(4-methoxy-benzyloxy)- 7.84 (dd, J = 8.4, 5.2 Hz, 2H); 6-morpholin-4-yl-7.40 (d, J = 8.3 Hz, 2H); 7.37 (s, 1H); benzofuran-3- 7.15 (t, J = 8.4Hz, 2H); 7.06 (s, carboxylic acid 1H); 6.93 (d, J = 8.8 Hz, 2H);methylamide 5.82 (d, J = 3.9 Hz, 1H); 5.09 (s, 2H); 3.85 (t, J = 4.4 Hz,4H); 3.82 (s, 3H); 3.11 (t, J = 4.4 Hz, 4H); 2.97 (d, J = 4.8 Hz, 3H)31. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 619 A <1[methanesulfonyl-(4- 8.38 (d, J = 4.1 Hz, 1H); 7.88 (dd,methoxy-benzyl)- J = 8.4, 5.2 Hz, 2H); 7.48 (d, amino]-5-(4-methoxy- J =8.8 Hz, 2H); 7.34 (t, J = 8.8 Hz, benzyloxy)-benzofuran- 2H); 7.29 (s,1H); 7.28 (s, 1H); 3-carboxylic acid 7.12 (d, J = 8.8 Hz, 2H); 7.00 (d,methylamide J = 8.2 Hz, 2H); 6.79 (d, J = 8.8 Hz, 2H); 5.13 (s, 2H);4.60 (br m, 2H); 3.77 (s, 3H); 3.66 (s, 3H); 2.94 (s, 3H); 2.80 (d, J =4.7 Hz, 3H) 32. 5-Ethoxy-6-(ethyl- ¹H NMR in DMSO: (M + H)⁺ = 435 A <1methanesulfonyl- 8.41 (d, J = 4.1 Hz, 1H); 7.94 (dd, amino)-2-(4-fluoro-J = 8.2, 5.3 Hz, 2H); 7.55 (s, 1H); phenyl)-benzofuran-3- 7.36 (t, J =8.2 Hz, 2H); 7.16 (s, carboxylic acid 1H); 4.14 (q, J = 7.0 Hz, 2H);methylamide 3.62 (q, J = 7.0 Hz, 2H); 3.01 (s, 3H); 2.82 (d, J = 4.7 Hz,3H); 1.38 (t, J = 7.0 Hz, 3H); 1.05 (t, J = 7.0 Hz, 3H) 33.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 468 A <1morpholin-4-yl-5- 8.35 (d, J = 4.4 Hz, 1H); (thiazol-2-ylmethoxy)-7.95-7.80 (m, 4H); 7.35-7.25 (m, 4H); benzofuran-3- 5.49 (s, 2H); 3.78(m, 4H); 3.06 (m, carboxylic acid 4H); 2.83 (d, J = 4.4 Hz, 3H)methylamide 34. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 477 A<1 isopropoxy-6- 8.38 (d, J = 4.8 Hz, 1H); 7.94 (dd,[methanesulfonyl-(2- J = 8.4, 5.3 Hz, 2H); 7.71 (s, 1H);oxo-propyl)-amino]- 7.36 (t, J = 8.8 Hz, 2H); benzofuran-3- 7.15 (s,1H); 4.77 (septet, J = 6.1 Hz, carboxylic acid 1H); 4.04 (s, 2H); 3.04(s, 3H); methylamide 2.81 (d, J = 4.4 Hz, 3H); 2.11 (s, 3H); 1.36 (d, J= 6.1 Hz, 6H) 35. 2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ = 468A <1 morpholin-4-yl-5- 8.84 (d, 1H, J = 1.76); 7.88 (m,(thiazol-4-ylmethoxy)- 2H); 7.44 (s, 2H); 7.17 (t, 2H, benzofuran-3- J =8.79); 7.10 (s, 1H); 5.77 (brs, carboxylic acid 1H); 5.37 (s, 2H); 3.89(m, 4H); methylamide 3.16 (m, 4H); 3.00 (d, 3H, J = 4.69) 36.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 518 A <1isopropoxy-6- 8.69 (d, 1H, J = 2.20 Hz); (methanesulfonyl- 7.77 (m, 2H);7.40 (s, 1H); thiazol-4-ylmethyl- 7.37 (s, 1H); 7.30 (d, 1H, J = 2.20Hz); amino)-benzofuran-3- 7.18 (t, 2H, J = 8.79 Hz); carboxylic acid5.67 (brs, 1H); 5.03 (brs, 2H); methylamide 4.79 (m, 1H); 3.07 (s, 3H);2.95 (d, 3H, J = 4.84 Hz); 1.44 (d, 6H, J = 5.72 Hz) 37.2-(4-Fluoro-phenyl)-6- ¹H NMR in CD₃OD: (M + H)+ = 425 A <1(5-hydroxymethyl- 7.94 (s, 1H); 7.92 (dd, J = 9.2, 5.3 Hz,isoxazol-3-yl)-5- 2H); 7.32 (s, 1H); isopropoxy-benzofuran- 7.25(apparent triplet, J = 8.8 Hz, 2H); 3-carboxylic acid 6.87 (s, 1H); 4.75(m, 1H); methylamide 4.72 (s, 2H); 2.95 (s, 3H); 1.39 (d, J = 5.7 Hz,6H) 38. 5-Ethoxy-2-(4-fluoro- ¹H NMR in DMSO: (M + H)⁺ = 421 A <1phenyl)-6- 8.39 (d, J = 4.0 Hz, 1H); 7.92 (dd, (methanesulfonyl- J =8.8, 5.3 Hz, 2H); 7.59 (s, 1H); methyl-amino)- 7.36 (t, J = 8.8 Hz, 2H);7.17 (s, benzofuran-3-carboxylic 1H); 4.16 (q, J = 7.0 Hz, 2H); acidmethylamide 3.19 (s, 3H); 3.01 (s, 3H); 2.81 (d, J = 4.4 Hz, 3H); 1.40(t, J = 7.0 Hz, 3H) 39. 4-[2-(4-Fluoro-phenyl)- ¹H NMR in DMSO: (M − H)⁻= 541 A <10 6-(methanesulfonyl- 8.39 (brd, 1H, J = 4.69 Hz);methyl-amino)-3- 7.93 (m, 2H); 7.84 (d, 1H, methylcarbamoyl- J = 8.21Hz); 7.72 (s, 1H); 7.39 (t, benzofuran-5- 2H, J = 8.79 Hz); 7.30 (s,1H); yloxymethyl]-2-hydroxy- 7.12 (m, 2H); 5.27 (s, 2H); benzoic acid3.24 (s, 3H); 3.00 (s, 3H); 2.83 (d, 3H, J = 4.69 Hz) 40.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 397.0 A <1(5-hydroxymethyl- 8.44 (brq, J = 4.83 Hz, 1H); isoxazol-3-yl)-5- 7.97(m, 3H); 7.39 (t, J = 8.79 Hz, 2H); methoxy-benzofuran-3- 7.29 (s, 1H);6.80 (d, carboxylic acid J = 0.879 Hz, 1H); 5.66 (t, J = 6.15methylamide & 5.71 Hz, 1H); 4.63 (d, J = 6.15 Hz, 2H); 3.93 (s, 3H);2.86 (d, J = 4.39 Hz, 3H) 41. 2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃:(M + H)⁺ = 411 A <1 [4-(2-hydroxy-ethyl)- 8.40 (s, 1H); 7.86 (dd, J =5.27, isoxazol-3-yl]-5- 8.79 Hz, 2H); 7.52 (s, 1H);methoxy-benzofuran-3- 7.45 (s, 1H); 7.20 (t, J = 8.35, 8.79 Hz,carboxylic acid 2H); 5.81 (brs, 1H); 3.87 (s, methylamide 3H); 3.69 (q,J = 6.15 Hz, 2H); 3.00 (d, J = 4.83 Hz, 3H); 2.64 (t, J = 6.15 Hz, 2H);1.45 (t, J = 5.27, 5.71 Hz, 1H). 42. 2-(4-Fluoro-phenyl)-6- ¹H NMR inDMSO: (M + H)⁺ = 437 A <1 [(2-hydroxy-ethyl)- 8.49 (d, J = 4.84 Hz, 1H);methanesulfonyl-amino]- 7.96-7.90 (m, 2H); 7.66 (s, 1H);5-methoxy-benzofuran-3- 7.41 (t, J = 7.03 Hz, 2H); 7.2 (s, 1H);carboxylic acid 4.75 (t, J = 5.71 Hz, 2H); 3.91 (s, methylamide 3H);3.44 (brs, 1H); 3.41 (d, J = 5.27 Hz, 2H); 3.05 (s, 3H); 2.84 (d, J =4.39 Hz, 3H) 43. 5-Cyclopropyl-2-(4- ¹H NMR in CDCl₃: (M + H)⁺ = 447 A<1 fluoro-phenyl)-6-[(2- 7.90-7.85 (m, 2H); 7.55 (s, 1H);hydroxy-ethyl)- 7.35 (s, 1H); 7.22-7.16 (m, 2H); methanesulfonyl-amino]-5.74 (brs, 1H); 4.09-4.03 (m, benzofuran-3-carboxylic 1H); 3.75 (s, 3H);3.14 (s, 3H); acid methylamide 2.99 (d, J = 4.40 Hz, 3H); 2.40-2.30 (m,1H); 1.95 (m, 1H); 1.10-0.98 (m, 2H); 0.88 (m, 1H); 0.68 (m, 1H) 44.5-Ethyl-2-(4-fluoro- ¹H NMR in DMSO: (M + H)⁺ = 391 A <10 phenyl)-6-9.20 (brs, 1H); 8.61 (m, 1H); methanesulfonylamino- 7.93 (dd, J = 5.3 &8.8 Hz, 2H); benzofuran-3- 7.60 (s, 1H); 7.48 (s, 1H); carboxylic acid7.37 (t, J = 8.8 Hz, 2H); 3.05 (s, 3H); methylamide 2.83 (d, J = 4.7 Hz,3H); 2.81 (q, J = 7.7 Hz, 2H); 1.21 (t, J = 7.7 Hz, 3H) 45.5-Ethyl-2-(4-fluoro- ¹H NMR in DMSO: (M + H)⁺ = 405 A <1 phenyl)-6- 8.50(m, 1H); 7.94 (dd, J = 5.3 & (methanesulfonyl- 8.8 Hz, 2H); 7.89 (s,1H); methyl-amino)- 7.54 (s, 1H); 7.60 (t, J = 8.8 Hz, 2H);benzofuran-3-carboxylic 3.29 (q, J = 7.0 Hz, 2H); 3.21 (s, acidmethylamide 3H); 3.13 (s, 3H); 2.83 (d, J = 4.7 Hz, 3H); 1.21 (t, J =7.0 Hz, 3H) 46. 5-Ethyl-2-(4-fluoro- ¹H NMR in DMSO: (M + H)⁺ = 435 A <1phenyl)-6-[(2-hydroxy- 8.45 (m, 1H); 7.94 (dd, J = 5.3 &ethyl)-methanesulfonyl- 9.4 Hz, 2H); 7.81 (s, 1H); amino]-benzofuran-3-7.55 (s, 1H); 7.39 (t, J = 8.8 Hz, 2H); carboxylic acid 3.72 (m, 1H);3.58 (m, 1H); methylamide 3.4 (m, 3H); 3.15 (s, 3H); 2.84 (d, J = 4.7Hz, 3H); 2.82 (q, J = 7.0 Hz, 2H); 1.25 (t, J = 7.0 Hz, 3H) 47.6-(1-Acetyl-pyrrolidin-2- ¹H NMR in CDCl₃: (M − H)⁻ = 411.1 A <1yl)-2-(4-fluoro-phenyl)- 7.85 (m, 2H); 7.36 (s, 1H);5-methoxy-benzofuran-3- 7.20 (m, 3H); 5.78 (brs, 1H); 5.40 (m,carboxylic acid 1H); 3.92 (s, 3H); 3.40-3.91 (m, methylamide 2H); 2.99(d, J = 4.8 Hz, 3H); 1.51-2.0 (m, 4H); 1.85 (s, 3H) 48.2-(4-Fluoro-phenyl)-5- ¹H NMR in (CD₃)₂CO: (M + H)⁺ = 385.0 A <10methoxy-6-(2-oxo- 8.03 (m, 2H); 7.68 (s, 1H); oxazolidin-5-yl)- 7.40(brs, 1H); 7.20-7.31 (4H); benzofuran-3-carboxylic 5.14 (m, 1H); 3.90(s, 3H); 3.60 (m, acid methylamide 1H); 3.38 (m, 1H); 2.94 (d, J = 4.8Hz, 3H) 49. 2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ = 358.1 A<1 (1-hydroxy-1-methyl- 7.85 (m, 2H); 7.50 (s, 1H); ethyl)-5-methoxy-7.39 (s, 1H); 7.20 (m, 2H); 5.75 (brs, benzofuran-3- 1H); 4.17 (s, 1H);3.99 (s, 3H); carboxylic acid 2.98 (d, J = 4.8 Hz, 3H); 1.66 (s,methylamide 6H) 50. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ =382 A <1 methoxy-6-(5-methyl- 8.12 (s, 1H); 7.90-7.86 (m, 2H);[1,2,4]oxadiazol-3-yl)- 7.48 (s, 1H); 7.24-7.18 (m, 2H); benzofuran-3-5.78 (s, 1H); 4.03 (s, 3H); 3.0 (d, carboxylic acid J = 4.8 Hz, 3H);2.67 (s, 3H) methylamide 51. 6-(3,5-Dimethyl- ¹H NMR in DMSO: (M + H)⁺ =439.0 A <1 isoxazol-4-yl)-2-(4- 8.41-8.43 (d, J = 4.69 Hz, 1H);fluoro-phenyl)-5-(3- 7.92-7.97 (m, 2H); 7.57 (s, 1H); hydroxy-propoxy)-7.35-7.41 (t, J = 8.79 Hz, 2H); benzofuran-3- 7.23 (s, 1H); 4.49-4.52(t, J = 5.28 Hz, carboxylic acid 1H); 4.06-4.11 (t, J = 6.45 Hz,methylamide 2H); 3.43-3.49 (q, J = 5.86 Hz, 2H); 2.84-2.86 (d, J = 4.69Hz, 3H); 2.29 (s, 3H) 52. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M +H)⁺ = 506 A <1 (methanesulfonyl- 8.40 (brd, J = 4.40 Hz, 1H);methyl-amino)-5-(2- 7.94 (m, 2H); 7.60 (s, 1H); 7.38 (t,morpholin-4-yl-ethoxy)- J = 8.79 Hz, 2H); 7.24 (s, 1H); benzofuran-3-4.21 (t, J = 5.28 Hz, 2H); 3.57 (m, carboxylic acid 4H); 3.23 (s, 3H);3.10 (s, 3H); methylamide 2.84 (d, J = 4.84 Hz, 3H); 2.76 (t, J = 5.28Hz, 2H); 2.48 (m, 4H). 53. 5-(Biphenyl-2- ¹H NMR in DMSO: (M + H)⁺ = 434C <30 ylmethoxy)-2-phenyl- 2.82 (d, 3H); 5.0 (s, 2H)benzofuran-3-carboxylic 6.96 (m, 1H); 7.32-7.96 (m, acid methylamide16H); 8.34 (d, 1H) 54. 5-Methoxy-2-(4- ¹H NMR in DMSO: *** B <10methoxy-phenyl)- 8.31 (br s, 1H); 7.82-7.84 (d, benzofuran-3-carboxylicJ = 7.03 Hz, 2H); acid methylamide 7.52-7.55 (d, J = 8.79 Hz, 1H);7.06-7.10 (m, 3H); 6.93-6.96 (dd, J = 2.35 Hz, 8.79 Hz, 1H); 3.83 (s,3H); 3.81 (s, 3H); 2.81-2.83 (d, J = 4.69 Hz, 3H) 55. 5-Methoxy-2-(3- ¹HNMR in DMSO: *** B <30 trifluoromethyl-phenyl)- 8.47-8.49 (d, J = 4.69Hz, 1H); benzofuran-3-carboxylic 8.19 (s, 1H); 8.15-8.18 (d, acidmethylamide J = 7.62 Hz, 1H); 7.74-7.84 (m, 2H); 7.61-7.64 (d, J = 9.38Hz, 1H); 7.13 (d, J = 2.34 Hz, 1H); 7.01-7.05 (dd, J = 2.34 Hz, 7.62 Hz,1H); 2.83-2.85 (d, J = 4.69 Hz, 3H) 56. 5-Methoxy-2-(4- ¹H NMR in DMSO:*** B <10 trifluoromethyl-phenyl)- 8.48-8.49 (d, J = 4.69 Hz, 1H);benzofuran-3-carboxylic 8.06-8.09 (d, J = 8.21 Hz, 2H); acid methylamide7.88-7.90 (d, J = 8.21 Hz, 2H); 7.61-7.64 (d, J = 8.79 Hz, 1H);7.12-7.13 (d, J = 2.93 Hz, 1H); 7.02-7.06 (dd, J = 2.93, 8.79 Hz, 1H);3.83 (s, 3H); 2.85-2.86 (d, J = 4.69 Hz, 3H) 57. 5-Ethoxy-2-phenyl- ¹HNMR in CDCl₃: (M + H)⁺ = 296 B >30 benzofuran-3-carboxylic 7.85 (dd,2H); 7.35-7.52 (m, acid methylamide 5H); 6.95 (d, 1H); 5.8 (s, br, 1H);4.14 (q, 2H); 2.97 (d, 3H) 1.41 (t, 3H) 58. 2-(2-Fluoro-phenyl)-5- ¹HNMR in DMSO: (M + H)⁺ = 300 B <10 methoxy-benzofuran-3- 8.05-8.07 (d, J= 4.69 Hz, 1H); carboxylic acid 7.72-7.77 (t of d, J = 1.76 Hz,methylamide 7.62 Hz, 1H); 7.52-7.63 (m, 2H); 7.37-7.39 (d, J = 7.62 Hz1H); 7.33-7.38 (m, 1H); 7.18-7.19 (d, J = 2.35 Hz, 1H); 6.99-7.03 (m,2H); 3.83 (s, 3H); 2.75-2.76 (d, J = 4.69 Hz, 3H) 59.5-Isopropoxy-2-phenyl- ¹H NMR in CDCl₃: (M + H)⁺ = 310 B <30benzofuran-3-carboxylic 7.87 (d, 2H); 7.52-7.37 (m, 5H); acidmethylamide 6.94 (d, 1H); 5.78 (s, br, 1H); 4.6 (m, 1H); 2.98 (d, 3H);1.38 (d, 6H) 60. 5-Butoxy-2-phenyl- ¹H NMR in CDCl₃: (M + H)⁺ = 324 B<30 benzofuran-3-carboxylic 7.87 (m, 2H), 7.51-7.3 (m, 5H); acidmethylamide 6.97 (d, 1H); 5.78 (s, br, 1H); 4.06 (m, 2H); 2.98 (d, 3H);1.83-1.54 (m, 4H); 1.02 (m, 3H) 61. 2-Phenyl-5-propoxy- ¹H NMR in CDCl₃:(M + H)⁺ = 310 B <30 benzofuran-3-carboxylic 7.86 (m, 2H); 7.5-7.27 (m,5H); acid methylamide 6.96 (dd, 1H); 5.76 (s, br, 1H); 3.99 (t, 2H);2.98 (d, 3H); 1.84 (m, 2H); (t, 3H) 62. 5-Methoxy-2-(2,4,5- ¹H NMR inDMSO: *** C <30 trifluoro-phenyl)- 8.08-8.09 (d, J = 4.69 Hz, 1H);benzofuran-3-carboxylic 7.86-7.95 (m, 1H); acid methylamide 7.71-7.80(m, 1H); 7.58-7.61 (d, J = 9.38 Hz, 1H); 7.22-7.23 (d, J = 2.35 Hz, 1H);7.02-7.06 (dd, J = 2.93 Hz, 9.38 Hz, 1H); 3.83 (s, 3H); 2.76-2.77 (d, J= 4.69 Hz, 3H) 63. 5-Methoxy-7-methyl-2- ¹H NMR in DMSO: (M + H)⁺ = 296B <10 phenyl-benzofuran-3- 8.33-8.34 (d, J = 4.69 Hz, 1H); carboxylicacid 7.87-7.89 (d, J = 7.62 Hz, 2H); methylamide 7.45-7.55 (m, 3H);6.89-6.90 (d, J = 2.34 Hz, 1H); 6.83-6.84 (d, J = 2.34 Hz, 1H); 3.80 (s,3H); 2.82-2.84 (d, J = 4.69 Hz, 3H); 2.50 (s, 3H) 64.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 368 B ***(2,2,2-trifluoro-ethoxy)- 8.06 (dd, 1H); 7.41 (dd, 2H);benzofuran-3-carboxylic 7.17 (m, 2H); 7.02 (dd, 1H); acid methylamide5.76 (m, br, 1H); 4.42 (q, 2H); 2.99 (d, 3H) 65. 2-(4-Fluoro-phenyl)-5-¹H NMR in CDCl₃: (M + H)⁺ = 328 B <30 isopropoxy-benzofuran- 7.90 (dd,2H); 7.29 (dd, 2H); 3-carboxylic acid 7.16 (dd, 1H); 6.92 (dd, 1H);methylamide 5.82 (s, br, 1H); 4.58 (m, 1H); 2.99 (d, 3H); 1.34 (s, 3H)66. 2-(2-Chloro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 315.9 C >30methoxy-benzofuran-3- 7.85-7.86 (d, J = 4.69 Hz, 1H); carboxylic acid7.47-7.69 (m, 5H); 7.27-7.28 (d, methylamide J = 2.34 Hz, 1H); 7.00-7.04(dd, J = 2.93 Hz, 9.38 Hz, 1H); 3.84 (s, 3H); 2.72-2.73 (d, J = 4.69 Hz,3H) 67. 6-Methoxy-2-phenyl- ¹H NMR in CDCl₃: (M + H)⁺ = 282 B <10benzofuran-3-carboxylic 7.86 (m, 2H); 7.73 (d, J = 8.87 Hz, acidmethylamide 1H); 7.51-7.42 (m, 3H); 7.04 (d, J = 2.4 Hz, 1H); 6.94 (d ofd, J = 8.8 Hz, 1H); 5.81 (br s, 1H); 3.87 (s, 3H); 2.98 (d, J = 4.7 Hz,3H) 68. 2-Furan-2-yl-5-methoxy- ¹H NMR in DMSO: M = 271 B <30benzofuran-3-carboxylic 8.28-8.29 (d, J = 4.10 Hz 1H); acid methylamide7.92 (s, 3H); 7.54-7.57 (d, J = 8.79 Hz, 1H); 7.18-7.19 (d, J = 3.52 Hz,1H); 7.15-7.16 (d, J = 2.35 Hz, 1H); 6.96-7.00 (dd, J = 2.35, 8.79 Hz,1H); 6.71-6.72 (m, 1H); 3.82 (s, 3H); 2.84-2.86 (d, J = 4.10 Hz, 3H) 69.2-(3-Fluoro-4-methyl- ¹H NMR in DMSO: (M + H)⁺ = 314 A <10phenyl)-5-methoxy- 8.42 (s, 1H); 7.63 (m, 3H); benzofuran-3-carboxylic7.43 (m, 1H); 7.09 (m, 1H); 7.00 (m, acid methylamide 1H); 3.82 (s, 3H);2.84 (d, J = 4.8 Hz, 3H); 2.30 (s, 3H) 70. 2-(4-Bromo-phenyl)-5- ¹H NMRin DMSO: (M + H)⁺ = 361 A <10 methoxy-benzofuran-3- 8.41 (m, 1H); 7.81(d, J = 7.5 Hz, carboxylic acid 2H); 7.72 (d, J = 8.4 Hz, 2H);methylamide 7.58 (d, J = 9.3 Hz, 1H); 7.09 (s, 1H); 7.01 (d, J = 8.7 Hz,1H); 3.82 (s, 3H); 2.83 (d, J = 4.2 Hz, 3H) 71. 2-(4-Fluoro-3-methyl- ¹HNMR in DMSO: (M + H)⁺ = 314 A <30 phenyl)-5-methoxy- 8.33 (m, 1H); 7.80(dd, J = 8.1, benzofuran-3-carboxylic 1.8 Hz, 1H); 7.75 (m, 1H); acidmethylamide 7.56 (d, J = 9.0 Hz, 1H); 7.29 (m, 1H); 7.09 (d, J = 2.4 Hz,1H); 6.97 (dd, J = 8.1, 2.1 Hz, 1H); 3.81 (s, 3H); 2.84 (d, J = 4.2 Hz,3H); 2.35 (s, 3H) 72. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ =314 A <10 methoxy-7-methyl- 8.3 (d, br, 1H); 7.94 (dd, 2H);benzofuran-3-carboxylic 7.35 (dd, 2H); 6.89 (d, 1H), acid methylamide6.81 (d, 1H); 3.83 (s, 3H); 2.80 (d, 3H); 2.47 (s, 3H) 73.5-Chloro-2-(4-fluoro- ¹H NMR in CDCl₃: (M + H)⁺ = 304.27, B <10phenyl)-benzofuran-3- 7.96-7.91 (m, 2H); 7.81 (d, 306.13 carboxylic acidJ = 2.4 Hz, 1H); 7.42 (d, J = 8.7 Hz, methylamide 1H); 7.30 (d, d, J =2.4, 8.7 Hz, 1H); 7.21-7.16 (m, 2H); 5.789 (s, 1H); 3.01 (d, J = 4.8 Hz,3H) 74. 5-tert-Butyl-2-phenyl- ¹H NMR in CDCl₃: (M + H)⁺ = 308 A <10benzofuran-3-carboxylic 7.87-7.84 (m, 3H); acid methylamide 7.52-7.39(m, 5H); 5.79 (br s, 1H); 2.99 (d, J = 4.7 Hz, 3H); 1.39 (s, 9H) 75.5-Chloro-2-p-tolyl- ¹H NMR in CDCl₃: (M + H)⁺ = 300 A <10benzofuran-3-carboxylic 7.90 (d, J = 1.8 Hz, 1H); 7.75 (d, acidmethylamide J = 7.8 Hz, 2H); 7.43-7.40 (m, 1H); 7.32-7.27 (m, 3H); 2.97(d, J = 4.8 Hz, 3H); 2.43 (s, 3H) 76. 2-(3-Chloro-4-fluoro- ¹H NMR inCDCl₃: (M + H)⁺ = 334 B <10 phenyl)-5-methoxy- 8.62 (s, 1H); 8.08 (dd, J= 7.2, benzofuran-3-carboxylic 1.8 Hz, 1H); 7.88 (m, 1H); acidmethylamide 7.58 (m, 2H); 7.10 (d, J = 2.4 Hz, 1H); 6.98 (dd, J = 8.1,2.4 Hz, 1H); 3.82 (s, 3H); 2.84 (d, J = 4.8 Hz, 3H) 77.2-(4-Chloro-3-fluoro- ¹H NMR in CDCl₃: (M + H)⁺ = 334 A <10phenyl)-5-methoxy- 8.48 (s, 1H); 7.93 (d, J = 1.2 Hz,benzofuran-3-carboxylic 1H); 7.90 (m, 2H); 7.59 (d, acid methylamide J =9.0 Hz, 1H); 7.12 (d, J = 2.4 Hz, 1H); 7.04 (dd, J = 9.0, 2.4 Hz, 1H);3.82 (s, 3H); 2.85 (d, J = 4.5 Hz, 3H) 78. 5-Methoxymethyl-2- ¹H NMR inCDCl₃: (M + H)⁺ = 296 B <30 phenyl-benzofuran-3- 7.90 (d of d, J = 8.2Hz, 2H); carboxylic acid 7.83 (s, 1H); 7.51-7.42 (m, 4H); methylamide7.34 (d, J = 8.8 Hz, 1H); 5.83 (brs, 1H); 4.56 (s, 2H); 3.41 (s, 3H);3.00 (d, J = 4.7 Hz, 3H) 79. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CD₃OD:(M + H)⁺ = 342 A <10 isopropoxy-6-methyl- 7.85 (dd, 2H); 7.31 (s, 1H);benzofuran-3-carboxylic 7.20 (dd, 2H); 7.10 (s, 1H); 4.61 (m, acidmethylamide 1H); 2.92 (s, 3H); 2.29 (s, 3H); 1.37 (d, 6H) 80.2-(4-Fluoro-phenyl)-5- ¹H NMR in CD₃OD: (M + H)⁺ = 342 B <30 isopropoxy-7.85 (dd, 2H); 7.25 (d, 1H); 7-methyl-benzufuran-3- 7.20 (dd, 2H); 6.80(d, 1H); 4.61 (m, carboxylic acid 1H); 2.92 (s, 3H); 2.38 (s, 3H);methylamide 1.37 (d, 6H) 81. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃:(M + H)⁺ = 314 A <10 methoxy- 7.9 (dd, 2H); 7.26 (s, 1H);6-methyl-benzofuran-3- 7.22 (s, 1H); 7.16 (dd, 2H); 5.78 (s, carboxylicacid 1H, br); 3.89 (s, 3H); 2.98 (d, methylamide 3H); 2.33 (s, 3H) 82.5-Fluoro-2-(4-fluoro- ¹H NMR in CDCl₃: (M + H)⁺ = 288 B <30phenyl)-benzofuran-3- 7.93-7.88 (m, 2H); 7.48 (dd, carboxylic acid J =2.7 Hz, 8.4 Hz, 1H); 7.41 (dd, methylamide J = 3.9 Hz, 8.7 Hz, 1H);7.21-7.14 (m, 2H); 7.06 (td, J = 2.7 Hz, 8.7 Hz, 1H); 5.86 (s, 1H); 2.98(d, J = 4.8 Hz, 3H) 83. 2-(4-Ethyl-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺= 298 A <10 fluoro-benzofuran-3- 7.77 (d, J = 7.8 Hz, 2H); 7.59 (dd,carboxylic acid J = 2.7 Hz, 8.4 Hz, 1H); 7.41 (dd, methylamide J = 4.5Hz, 8.7 Hz, 1H); 7.33 (d, J = 8.4 Hz, 2H); 7.03 (td, J = 2.4 Hz, 8.7 Hz,1H); 5.79 (s, 1H); 2.96 (d, J = 5.1 Hz, 3H); 2.72 (q, J = 7.8 Hz, 15.3Hz, 2H); 1.29 (t, J = 7.5 Hz, 3H) 84. 5-Ethyl-2-phenyl- ¹H NMR in CDCl₃:(M + H)⁺ = 280 B <30 benzofuran-3-carboxylic 7.89 (m, 3H); 7.70 (s, 1H);acid methylamide 7.5-7.37 (m, 3H); 7.15 (m, 1H); 5.81 (br s, 1H); 3.0(d, 3H); 2.76 (q, 2H); 1.25 (t, 3H) 85. 2-(5-Chloro-thiophen-2- ¹H NMRin DMSO: (M + H)⁺ = 322 A <10 yl)-5-methoxy- 8.32 (s, 1H); 7.67 (d, J =4.2 Hz, benzofuran-3-carboxylic 1H); 7.54 (d, J = 9.0 Hz, 1H); acidmethylamide 7.22 (d, J = 4.2 Hz, 1H); 7.15 (s, 1H); 6.98 (d, J = 6.9 Hz,1H); 3.81 (s, 3H); 2.84 (d, J = 4.5 Hz, 3H) 86. 5-Isopropyl-2-phenyl- ¹HNMR in CDCl₃: (2M + Na)⁺ = 609.2 A <10 benzofuran-3-carboxylic 7.87 (m,2H); 7.74 (s, 1H); acid methylamide 7.54-7.43 (m, 4H); 7.27-7.23 (m,1H); 5.82 (br s, 1H); 3.10-3.00 (m + d, 4H); 1.33 (d, 6H) 87.2-(5-Chloro-thiophen-2- ¹H NMR in CDCl₃: (M + H)⁺ = 336 A <10yl)-5-ethoxy-benzofuran- 7.72 (d, J = 3.6 Hz, 1H); 7.38 (d, 3-carboxylicacid J = 8.1 Hz, 1H); 7.14 (d, J = 2.4 Hz, methylamide 1H); 6.95 (d, J =3.9 Hz, 1H); 6.92 (d, J = 2.4 Hz, 1H); 5.98 (s, 1H) 4.10 (q, 2H); 3.07(d, J = 4.5 Hz, 3H); 1.45 (t, 3H) 88. 5-Methoxy-2-thiophen-2- ¹H NMR inDMSO: (M + H)⁺ = 288 B <30 yl-benzofuran-3- 8.38 (s, 1H), 7.83 (d, J =3.3 Hz, carboxylic acid 1H); 7.76 (d, J = 5.4 Hz, 1H); methylamide 7.55(d, J = 9.0 Hz, 1H); 7.21 (m, 1H); 7.11 (d, J = 2.1 Hz, 1H); 6.97 (dd, J= 9.0, 2.4 Hz, 1H); 3.82 (s, 3H); 2.86 (d, J = 4.5 Hz, 3H) 89.5-Chloro-2-pyridin-3-yl- ¹H NMR in CDCl₃: (M + H)⁺ = 286.9 B >30benzofuran-3-carboxylic 9.15-9.14 (m, 1H); acid methylamide 8.68-8.66(m, 1H); 8.33-8.29 (m, 1H); 7.77 (d, J = 2.1 Hz, 1H); 7.49-7.39 (m, 2H);7.34 (dd, J = 2.1 Hz, 8.7 Hz, 1H); 6.0 (s, 1H); 3.04 (d, J = 4.8 Hz, 3H)90. 2-(4-Bromo-3-fluoro- ¹H NMR in DMSO: (M + H)⁺ = 406 A <10phenyl)-5-isopropoxy- 8.45 (d, J = 3.9 Hz, 1H); 7.88 (dd,benzofuran-3-carboxylic J = 8.4, 2.4 Hz, 1H); 7.85 (d, acid methylamideJ = 3.0 Hz, 1H); 7.67 (dd, J = 9.0, 1.8 Hz, 1H); 7.57 (d, J = 8.1 Hz,1H); 7.10 (d, J = 2.4 Hz, 1H); 7.02 (dd, J = 9.3, 2.7 Hz, 1H); 4.64 (m,1H); 2.84 (d, J = 4.8 Hz, 3H); 1.29 (d, J = 6.0 Hz, 6H) 91.2-(2,4-Difluoro-phenyl)- ¹H NMR in DMSO: (M + H)⁺ = 345 A <305-isopropoxy- 8.04 (d, J = 7.2 Hz, 1H); 7.82 (d, benzofuran-3-carboxylicJ = 6.3 Hz, 1H); 7.56 (d, J = 9.3 Hz, acid methylamide 1H); 7.46 (d, J =9.3 Hz, 1H); 7.30 (d, J = 2.4 Hz, 1H); 7.20 (d, J = 2.1 Hz, 1H); 6.99(dd, J = 8.1, 2.4 Hz, 1H); 4.61 (m, 1H); 2.75 (d, J = 4.8 Hz, 3H); 1.30(d, J = 6.0 Hz, 6H) 92. 6-Bromo-2-(4-fluoro- *** (M + H)⁺ = 406 A <1phenyl)-5-isopropoxy- benzofuran-3-carboxylic acid methylamide 93.5-Methoxy-2-(4- ¹H NMR in CDCl₃: (M + H)⁺ = 367 B >30morpholin-4-yl-phenyl)- 7.76 (dd, J = 4.8, 3.0 Hz, 2H);benzofuran-3-carboxylic 7.37 (m, 2H); 6.97 (dd, J = 9.0, acidmethylamide 1.8 Hz, 2H); 6.89 (dd, J = 8.1, 2.1 Hz, 1H); 5.84 (m, 1H);3.87 (s, 3H); 3.88 (t, 4H); 3.27 (t, 4H); 2.96 (d, J = 5.4 Hz, 3H) 94.5,6-Dimethoxy-2-phenyl- ¹H NMR in CDCl₃: (M + H)⁺ = 312 A <1benzofuran-3-carboxylic 7.79 (d, 6.4 Hz, 2H); acid methylamide 7.52-7.40(m, 3H); 7.38 (s, 1H); 7.06 (s, 1H); 5.78 (brs, 1H); 3.96 (s, 3H); 3.94(s, 3H); 2.96 (d, J = 4.7 Hz, 3H) 95. 5-Isopropoxy-2-(4- ¹H NMR in DMSO:(M + H)⁺ = 379 C <30 pyrrolidin-1-yl-phenyl)- 8.16 (s, 1H); 7.71 (d, J =8.1 Hz, benzofuran-3-carboxylic 2H); 7.45 (d, J = 8.1 Hz, 1H); acidmethylamide 7.01 (d, J = 1.8 Hz, 1H); 6.85 (dd, J = 8.1, 2.1 Hz, 1H);6.62 (d, J = 8.1 Hz, 2H); 4.58 (m, 1H); 2.81 (d, J = 3.9 Hz, 3H); 2.00(m, 4H); 1.38 (d, J = 6.0 Hz, 6H) 96. 5-Fluoro-2-pyridin-4-yl- ¹H NMR inCDCl₃: (M + H)⁺ = 271 B >30 benzofuran-3-carboxylic 8.75-8.73 (m, 2H);acid methylamide 7.87-7.84 (m, 2H); 7.53-7.43 (m, 2H); 7.18-7.10 (m,1H); 5.92 (brs, 1H); 3.09 (d, J = 4.8 Hz, 3H) 97.2-[2-(4-Fluoro-phenyl)- ¹H NMR in acetic-d₃ acid-d (M + H)⁺ = 371 C >306-methyl-3- (CD₃CO₂D): methylcarbamoyl- 8.75-8.73 (m, 2H);benzofuran-5-yloxy]- 7.87-7.84 (m, 2H); 7.53-7.43 (m, 2H); propionicacid 7.18-7.10 (m, 1H); 5.92 (brs, 1H); 3.09 (d, J = 4.8 Hz, 3H) 98.6-Acetylamino-2-(4- ¹H NMR in CDCl₃: (M + H)⁺ = 85 A <10fluoro-phenyl)-5- 8.66 (s, 1H); 7.99 (s, 1H); isopropoxy-benzofuran-7.82 (dd, 2H, J = 5.2 & 8.7 Hz); 3-carboxylic acid 7.37 (s, 1H); 7.18(t, 2H, J = 8.7 Hz); methylamide 5.78 (brs, 1H); 4.70 (heptuplet, J =6.1 Hz); 2.96 (d, 3H, J = 4.9 Hz); 2.24 (s, 3H); 1.41 (d, 6H, J = 6.1Hz) 99. 2-(4-Amino-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 325 B <30isopropoxy-benzofuran- 7.64-7.67 (d, J = 8.79 Hz, 2H); 3-carboxylic acid7.41-7.42 (d, J = 2.93 Hz, 1H); methylamide 7.32-7.35 (d, J = 8.79 Hz,1H); 6.86-6.90 (dd, J = 2.33 Hz, 8.79 Hz, 1H); 6.74-6.77 (d, J = 7.03Hz, 2H); 5.84 (br.s, 1H); 4.56-4.64 (septet, J = 6.45 Hz, 1H); 2.96-2.97(d, J = 4.69 Hz, 3H); 1.35-1.37 (d, J = 6.45 Hz, 6H) 100.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 456 B <30isopropoxy-6-(2- 8.22-8.24 (d, J = 4.69 Hz, 1H); morpholin-4-yl-7.82-7.87 (m, 2H); 7.28-7.34 (t, ethylamino)-benzofuran- J = 8.79 Hz,2H); 6.98 (s, 1H); 3-carboxylic acid 6.79 (s, 1H); 5.28 (brs, 1H);methylamide 4.56 (brs, 1H); 3.60 (brs, 3H); 3.23 (brs, 3H); 2.81-2.82(d, J = 4.69 Hz, 3H); 2.61 (brs, 1H); 2.43 (brs, 3H); 1.31-1.33 (d, J =5.86 Hz, 6H) 101. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 411A <1 isopropoxy-6-piperidin- 7.89-7.84 (m, 2H); 7.23 (s, 1H);1-yl-benzofuran-3- 7.14 (t, J = 8.79, 2H); 7.04 (s, carboxylic acid 1H);5.78 (brs, 1H); methylamide 4.69-4.29 (septet, J = 6.15, 1H); 3.05-3.01(m, 4H); 2.98 (d, J = 5.27, 3H); 1.77-1.72 (m, 4H); 1.60-1.59 (m, 2H);1.36 (d, J = 6.15, 6H) 102. 2-(4-Fluoro-phenyl)-5,6- ¹H NMR in CDCl₃:(M + H)⁺ = 330 A <1 dimethoxy-benzofuran-3- 7.85-7.81 (m, 2H); 7.32 (s,1H); carboxylic acid 7.25-7.20 (m, 2H); 7.05 (s, 1H); methylamide 5.75(brs, 1H); 3.96 (s, 3H); 3.947 (s, 3H); 2.98 (d, J = 4.2 Hz, 3H) 103.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 385 A <1methoxy-6-morpholin-4- 7.85-7.81 (m, 2H); 7.30 (s, 1H); yl-benzofuran-3-7.17 (t, J = 8.8 Hz, 2H); 7.08 (s, carboxylic acid 1H); 3.94 (s, 3H);3.94-3.91 (m, methylamide 4H); 3.11-3.09 (m, 4H); 2.98 (d, J = 4.7 Hz,3H) 104. 2-(4-Bromo-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 288 A <10isopropoxy-benzofuran- 7.80 (d, 2H, J = 8.79); 7.61 (d, 3-carboxylicacid 2H, J = 8.79); 7.39 (d, 1H, methylamide J = 8.79); 7.28 (d, 1H, J =2.34); 6.94 (dd, 1H, J = 8.79, 2.34); 5.80 (brs, 1H); 4.58 (m, 1H); 3.01(d, 3H, J = 4.69); 1.36 (d, 6H, J = 6.45) 105. 2-(4-Fluoro-3-hydroxy- ¹HNMR in DMSO: (M + H)⁺ = 344 C <30 phenyl)-5-isopropoxy- 10.18 (brs, 1H);8.32 (d, 1H, benzofuran-3-carboxylic J = 4.69); 7.50 (m, 2H); 7.26 (m,acid methylamide 2H); 7.03 (d, 1H, J = 2.34); 6.93 (dd, 1H, J = 8.79,2.34); 4.58 (m, 1H); 2.81 (d, 3H, J = 4.69); 1.26 (d, 6H, J = 5.86) 106.2-(4-Cyano-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 335 B <30isopropoxy-benzofuran- 8.11 (d, 2H, J = 8.21); 7.74 (d, 3-carboxylicacid 2H, J = 8.79); 7.43 (d, 1H, methylamide J = 9.38); 7.20 (d, 1H, J =2.34); 7.00 (dd, 1H, J = 8.79, 2.34); 5.88 (brs, 1H); 4.58 (m, 1H); 3.06(d, 3H, J = 4.69); 1.36 (d, 6H, J = 6.45) 107. 5-Methoxy-2-pyridin-4- ¹HNMR in CDCl₃: (M + H)⁺ = 283 B <100 yl-benzofuran-3- 8.72 (d, J = 5.4H3,2H); 7.83 (dd, carboxylic acid J-1.8H3, 4.5H3, 2H); 7.45 (d, methylamideJ = 9.0H3, 1H); 7.20 (d, J = 2.2H3, 1H); 7.01 (dd, J = 2.7H3, 8.7H3,1H); 5.90 (brs, 1H); 3.88 (s, 3H); 3.08 (d, J = 4.8H3, 3H) 108.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 475 A <1isopropoxy-6-(3- 7.90 (dd, J = 1.8, 5.3 Hz, 2H); methanesulfonyl- 7.33(t, J = 8.8 Hz, 2H); 7.07 (s, pyrrolidin-1-yl)- 1H); 7.05 (s, 1H); 4.63(p, benzofuran-3-carboxylic J = 6.4 Hz, 1H); 3.96-3.86 (m, acidmethylamide 2H); 3.49-3.32 (m, 2H); 3.03 (s, 3H); 2.82 (s, 3H); 2.31 (m,2H); 1.33 (d, J = 1.2 Hz, 6H) 109. 6-Azetidin-1-yl-2-(4- ¹H NMR inCDCl₃: (M + H)⁺ = 383 A <1 fluoro-phenyl)-5- 7.82 (dd, J = 5.3, 8.8 Hz,2H); isopropoxy-benzofuran- 7.13 (s, 1H); 7.13 (t, J = 8.2 Hz,3-carboxylic acid 2H); 6.54 (s, 1H); 4.60 (p, methylamide J = 5.9 Hz,1H); 3.96 (t, J = 7.6 Hz, 4H); 2.97 (d, J = 5.3 Hz, 3H); 2.29 (p, J =7.0 Hz, 2H); 1.36 (d, J = 6.4 Hz, 6H) 110. 2-(4-Fluoro-phenyl)-6- ***(M + H)⁺ = 413 A <1 (3-hydroxy-pyrrolidin-1- yl)-5-isopropoxy-benzofuran-3-carboxylic acid methylamide 111. 2-(4-Fluoro-phenyl)-5- ¹HNMR in CDCl₃: (M + H)⁺ = 435 A <1 isopropoxy-6- 7.81 (2H, dd, J = 5.3,8.8 Hz); (methanesulfonyl- 7.56 (1H, s) methyl-amino)- 7.42 (1H, s);7.20 (2H, r, benzofuran-3-carboxylic J = 8.8 Hz); 5.70 (1H, brs); acidmethylamide 4.80 (1H, heptuplet, J = 6.2 Hz); 3.32 (3H, s); 2.98 (3H,s); 2.96 (3H, s); 1.42 (3H, d, J = 6.2 Hz) 112. 2-(4-Fluoro-phenyl)-6-¹H NMR in CDCl₃: (M + H)⁺ = 423 A <1 [(furan-3-ylmethyl)- 7.76-7.81 (m,2H); 7.37 (d, amino]-5-isopropoxy- J = 1.17, 1H); 7.17 (s, 1H);benzofuran-3-carboxylic 7.086-7.145 (t, J = 8.79, 2H); 6.746 (s, acidmethylamide 1H); 6.319-6.328 (m, 1H); 6.242-6.252 (d, J = 2.93, 1H);5.86 (brs, 1H); 4.565-4.645 (septet, J = 6.45, 1H); 4.365 (s, 2H);2.940-2.955 (d, J = 4.69, 3H); 1.375-1.254 (d, J = 6.45, 6H) 113.6-(2,3-Dihydroxy- ¹H NMR in CDCl₃: (M + H)⁺ = 417 B <10propylamino)-2-(4- 7.78 (brs, 2H); 7.12 (m, 4H); fluoro-phenyl)-5- 6.72(brs, 1H); 5.84 (d, J = 4.7 Hz, isopropoxy-benzofuran- 1H); 4.60 (p, J =5.9 Hz, 1H); 3-carboxylic acid 4.01 (m, 1H); 3.80 (dd, J = 3.52,methylamide 11.1 HZ, 1H); 3.66 (dd, J = 5.9, 11.1 Hz, 1H); 2.96 (d, J =4.7 Hz, 3H); 1.37 (dd, J = 1.8, 5.9 Hz, 6H) 114. 2-(4-Fluoro-phenyl)-5-¹H NMR in CDCl₃: (M + H)⁺ = 385 A <1 isopropoxy-6- 7.805-7.834 (m, 2H);7.151 (s, isopropylamino- 1H); 7.100-7.127 (m, 2H);benzofuran-3-carboxylic 6.680 (s, 1H); 5.960 (brs, 1H); acid methylamide4.580-4.600 (septet, J = 5.861, 1H); 3.662-3.686 (septet, J = 7.033,1H); 2.955-2.971 (d, J = 4.688, 3H); 2.057 (s, 1H); 1.361-1.381 (d, J =5.861, 6H); 1.258-1.277 (d, J = 5.861, 6H) 115. 6-(Cyclopropylmethyl- ¹HNMR in CDCl₃: (M + H)⁺ = 397 A <1 amino)-2-(4-fluoro- 7.780-7.866 (m,2H); 7.176 (s, phenyl)-5-isopropoxy- 1H); 7.104-7.160 (m, 2H);benzofuran-3-carboxylic 6.664 (s, 1H); 5.781 (br, 1H); acid methylamide4.567-4.647 (septet, J = 5.861, 1H); 3.000-3.024 (d, J = 7.033, 2H);2.965-2.981 (d, J = 4.689, 3H); 1.502-1.676 (m, 1H); 1.383-1.402 (m,1H); 1.211-1.172 (m, 1H); 0.557-0.619 (m, 1H); 0.262-.0311 (m, 1H) 116.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 369 A <1methoxy-6-pyrrolidin-1- 8.28 (d, J = 4.40, 1H); yl-benzofuran-3-7.89-7.84 (m, 2H); 7.31 (t, J = 8.79, 2H); carboxylic acid 7.00 (s, 1H);6.91 (s, 1H); methylamide 3.81 (s, 3H); 3.29 (m, 4H); 2.82 (d, J = 4.40,3H); 1.88 (m, 4H) 117. 5-Benzyloxy-2-(4-fluoro- ¹H NMR in CDCl₃: (M +H)⁺ = 461 A <1 phenyl)-6-morpholin-4- 7.788-7.83 (m, 2H);yl-benzofuran-3- 7.60-7.09 (m, 9H); 5.71 (brs, 1H); 5.19 (s, carboxylicacid 2H); 3.90-3.87 (m, 4H); methylamide 3.17-3.15 (m, 4H); 2.98 (d, J =51. Hz, 3H) 118. 5-Hydroxymethyl-2- ¹H NMR in CDCl₃: (M + H)⁺ = 282C >100 phenyl-benzofuran-3- 7.98-7.87 (m, 3H); carboxylic acid 7.53-7.43(m, 4H); 7.38 (d, J = 7.0 Hz, 1H); methylamide 5.84 (br s, 1H); 4.83 (d,J = 6.0 Hz, 2H); 2.99 (d, J = 5.3 Hz, 3H) 119. 2-(4-Fluoro-phenyl)-5- ¹HNMR in CDCl₃: (M + H)⁺ = 415 A <1 isopropoxy-6-[(2- 7.86-7.82 (m, 2H);methoxy-ethyl)-methyl- 7.26-7.24 (m, 1H); 7.15 (t, J = 8.35 Hz, 2H);amino]-benzofuran-3- 7.08 (s, 1H); 5.76 (s, 1H); carboxylic acid4.70-4.62 (septet, J = 6.15 Hz, 1H); methylamide 3.59 (t, J = 6.15 Hz,2H); 3.37-3.35 (m, 2H); 3.33 (s, 1H); 2.98 (d, J = 4.83 Hz, 3H); 2.92(s, 3H); 1.39 (d, J = 6.15 Hz, 6H) 120. 6-Amino-5-benzyloxy-2- ¹H NMR inCDCl₃: (M + H)⁺ = 391 A <10 (4-fluoro-phenyl)- 7.86-7.80 (m, 2H);benzofuran-3-carboxylic 7.45-7.33 (m, 5H); 7.287 (s, 1H); acidmethylamide 7.17-7.12 (m, 2H); 6.85 (s, 1H); 5.71 (brs, 1H); 5.15 (s,2H); 2.97 (d, J = 5.3 Hz, 3H) 121. 5-Isopropoxy-2-(3- ¹H NMR in CDCl₃:*** B <30 methyl-furan-2-yl)- 7.664-7.674 (d, J = 2.931, 1H);benzofuran-3-carboxylic 7.512-7.518 (d, J = 1.759, 1H); acid methylamide7.319-7.348 (d, J = 8.792, 1H); 6.893-6.932 (d of d, J = 2.931, 5.861,1H); 6.721 (brs, 1H); 6.448-6.453 (d, J = 1.759, 1H); 4.584-4.664(septet, J = 5.861, 1H); 3.006-3.024 (d, J = 5.275, 3H); 2.322 (s, 3H);1.344-1.363 (d, J = 5.861, 6H) 122. 2-(4-Fluoro-phenyl)-6- ¹H NMR inDMSO: (M + H)⁺ = 393 A <1 methanesulfonylamino-5- 8.37 (m, 1H); 7.93(dd, J = 5.1 methoxy-benzofuran-3- & 9.1 Hz, 2H); 7.56 (s, 1H);carboxylic acid 7.36 (t, J = 8.8 Hz, 2H); 7.17 (s, methylamide 1H); 3.90(s, 3H); 2.98 (s, 3H); 2.83 (d, J = 4.9 Hz, 3H) 123.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 427 A <10isopropoxy-6- 8.27 (d, br, 1H); 7.88 (dd, 2H); [(tetrahydro-furan-2-7.31 (dd, 2H), 6.92 (s, 1H), ylmethyl)-amino]- 6.84 (s, 1H); 4.98 (m,1H); 4.57 (m, benzofuran-3-carboxylic 1H); 4.11 (m, 1H); acidmethylamide 3.8-3.64 (m, 2H); 3.16 (m, 1H); 2.82 (d, 3H); 1.84-1.42 (m,4H); 1.35 (d, 6H) 124. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺= 370 B <10 hydroxy-6-morpholin-4- 8.00-7.95 (m, 2H); yl-benzofuran-3-7.36-7.26 (m, 2H); 7.21-7.18 (m, 2H); carboxylic acid 6.98 (brs, 1H);5.83 (brs, 1H); methylamide 3.95-3.92 (m, 4H); 3.04 (d, J = 5.1 Hz, 3H);2.97-2.96 (m, 4H) 125. 5-Cyclopropylmethoxy- ¹H NMR in CDCl₃: (M + H)⁺ =425 A <1 2-(4-fluoro-phenyl)-6- 7.89-7.84 (m, 2H); 7.30 (s,morpholin-4-yl- 1H); 7.22-7.16 (m, 2H); benzofuran-3-carboxylic 7.08 (s,1H); 5.76 (brs, 1H); acid methylamide 3.94-3.97 (m, 6H); 3.20-3.17 (m,2H); 3.01 (d, J = 4.8, 2H); 0.71-0.64 (m, 2H); 0.42-0.38 (m, 2H) 126.6-Chloro-2-(4-fluoro- ¹H NMR in CDCl₃: (M + H)⁺ = 334.0 A <1phenyl)-5-methoxy- 7.86-7.81 (m, 2H); 7.54 (s, benzofuran-3-carboxylic1H); 7.42 (s, 1H); 7.23-./16 (m, acid methylamide 2H); 5.77 (brs, 1H);3.96 (S, 3H); 2.98 (d, J = 4.7 Hz, 3H) 127. 6-(2,5-Dimethyl-2H- ¹H NMRin CDCl₃: (M + H)⁺ = 437.0 C *** pyrazol-3-ylamino)-2-(4- 7.782-7.826(m, 2H); 7.352 (s, fluoro-phenyl)-5- 1H); 7.137-7.194 (m, 2H);isopropoxy-benzofuran- 6.840 (s, 1H); 6.069 (s, 1H); 5.930 (s,3-carboxylic acid 1H); 5.795 (brs, 1H); methylamide 4.686-4.746 (septet,J = 6.447, 1H); 3.695 (s, 3H); 2.986-3.004 (d, J = 5.275, 3H); 2.287 (s,1H); 1.645 (brs, 2H); 1.436-1.457 (d, J = 6.447, 3H) 128.2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ = 462 A ***morpholin-4-yl-5- 8.68-8.65 (m, 2H); (pyridin-4-ylmethoxy)- 7.87-7.82(m, 2H); 7.40-7.43 (m, 3H); benzofuran-3-carboxylic 7.25-7.15 (m, 3H);5.70 (brs, acid methylamide 1H); 5.23 (3, 2H): 3.98-3.92 (m, 4H);3.15-3.21 (m, 4H): 2.99 (d, J = 48 Hz, 3H) 129. 6-Cyano-2-(4-fluoro- ¹HNMR in CDCl₃: (M + H)⁺ = 353 A *** phenyl)-5-isopropoxy- 7.87-7.82 (m,2H): 7.67 (s, 1H); benzofuran-3-carboxylic 7.45 (s, 1H); 7.26-7.19 (m,2H); acid methylamide 5.73 (brs, 1H); 4.75-4.67 (m, 1H); 2.98 (d, J =4.8 Hz, 3H); 1.43 (d, J = 6.3 Hz, 6H) 130. 5-Methoxy-2-phenyl- ¹H NMR inCDCl₃: (M + H)⁺ = 295 C <10 benzofuran-3-carboxylic 7.86 (dd, J = 2.1,7.4 Hz, 2H); acid ethylamide 7.47 (m, 3H); 7.39 (m, 2H); 5.78 (brs, 1H);3.88 (s, 3H); 6.94 (dd, J = 2.6, 9.0 Hz, 1H); 3.48 (dq, J = 1.3, 7.2 Hz,2H); 1.17 (t, 7.2 Hz, 3H) 131. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃:(M + H)⁺ = 420 B <30 isopropoxy-6-(pyridin-4- 8.29-8.31 (d, 2H, J = 5.86Hz); ylamino)-benzofuran-3- 7.80-7.84 (m, 2H); 7.51 (s, 1H); carboxylicacid 7.36 (s, 1H); 7.13-7.19 (t, 2H, methylamide J = 8.21 Hz); 6.95-6.98(m, 2H); 6.62 (s, 1H); 6.13-6.15 (d, 1H, J = 4.69 Hz); 4.60-4.68(septet, 1H, J = 5.86 Hz); 2.97-2.99 (d, 3H, J = 5.28 Hz); 1.37-1.39 (d,6H, J = 5.86 Hz) 132. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ =426 C >30 isopropoxy-6-(4-methyl- 7.80-7.86 (m, 2H); 7.21 (s, 1H);piperazin-1-yl)- 7.09-7.15 (t, 2H, J = 8.79 Hz); benzofuran-3-carboxylic6.99 (s, 1H); 6.12-6.14 (d, 1H, acid methylamide J = 4.69 Hz); 4.58-4.66(septet, 9H, J = 6.45 Hz); 3.10 (brs, 4H); 2.95-2.96 (d, 3H, J = 4.69Hz); 2.58 (brs, 4H); 2.34 (s, 3H); 1.34-1.36 (d, 6H, J = 6.45 Hz) 133.6-(3-Chloro-propane-1- ¹H NMR in DMSO: (M − H)⁻ = 481; B <1sulfonylamino)-2-(4- 9.11 (s, 1H); 8.37 (m, 1H); 483 fluoro-phenyl)-5-7.92 (dd, J = 8.8& 5.7 Hz, 2H); isopropoxy-benzofuran- 7.56 (s, 1H);7.36 (t, J = 8.8 Hz, 2H); 3-carboxylic acid 7.16 (s, 1H); 4.74(heptuplet, J = 5.7 Hz, methylamide 1H); 3.74 (t, J = 6.6 Hz, 2H); 3.21(m, 2H); 2.82 (d, J = 4.8 Hz, 3H); 2.21 (m, 2H); 1.35 (d, J = 5.7 Hz,6H) 134. 6-(1,1-Dioxido- ¹H NMR in DMSO: (M + H)⁺ = 447 B <10isothiazolidin-2-yl)-2-(4- 8.40 (m, 1H); 7.92 (dd, J = 5.5 dfluoro-phenyl)-5- 9.2 Hz, 2H); 7.60 (s, 1H); isopropoxy-benzofuran- 7.37(t, J = 9.2 Hz, 2H); 7.19 (s, 1H); 3-carboxylic acid 4.69 (heptuplet, J= 5.9 Hz, 1H); methylamide 3.75 (t, J = 7.0 Hz, 2H); 3.37 (m, 2H); 2.82(d, J = 4.9 Hz, 3H); 2.43 (p, J = 7.0 Hz, 2H); 1.34 (d, J = 5.9 Hz, 6H)135. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 486 A <10isopropoxy-6-ureido- 8.38 (s, 1H); 8.28 (m, 1H); benzofuran-3-carboxylic7.87 (dd, J = 5.3 & 9.2 Hz, 2H); acid methylamide 7.30 (t, J = 8.8 Hz,2H); 7.09 (s, 1H); 6.39 (brs, 2H); 4.62 (heptuplet, J = 6.1 Hz, 1H);2.80 (d, J = 4.8 Hz, 3H); 1.88 (s, 1H); 1.32 (d, J = 5.7 Hz, 6H) 136.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 463 A <1 isopropoxy-6-8.40 (m, 1H); 7.90 (dd, J = 5.3 & (isopropyl- 8.84 Hz, 2H); 7.69 (s,1H); methanesulfonyl- 7.36 (t, J = 8.8 Hz, 2H); 7.11 (s, 1H);amino)-benzofuran-3- 4.75 (heptuplet, J = 6.6 Hz, 2H); carboxylic acid4.22 (heptuplet, J = 7.1 Hz, 1H); methylamide 3.06 (s, 3H); 2.80 (d, J =7.1 Hz, 3H); 1.32 (t, J = 6.6 Hz, 6H); 1.20 (d, J = 7.1 Hz, 3H); 1.05(d, J = 7.1 Hz, 3H) 137. 6-(Cyclopropylmethyl- ¹H NMR in DMSO: (M + H)⁺= 475 A <1 methanesulfonyl- 8.44 (m, 1H); 7.94 (dd, J = 5.1 &amino)-2-(4-fluoro- 9.1 Hz, 2H); 7.57 (s, 1H); phenyl)-5-isopropoxy-7.38 (t, J = 8.8 Hz, 2H); 7.16 (s, 1H); benzofuran-3- 6.78 (heptuplet, J= 5.7 Hz, 1H); carboxylic acid 3.01 (s, 3H); 2.83 (d, J = 4.4 Hz,methylamide 3H); 1.33 (d, J = 5.7 Hz, 6H); 0.85 (m, 1H); 0.37 (m, 2H)138. 6-(2,6-Dimethyl- ¹H NMR in CDCl₃: (M + H)⁺ = 441 B <10morpholin-4-yl)-2-(4- 7.89-7.84 (m, 2H); 7.28 (d, fluoro-phenyl)-5- J =8.79 Hz, 1H); 7.17 (T, J = 8.79 Hz, isopropoxy-benzofuran- 2H); 7.04 (s,1H); 5.77 (s, 3-carboxylic acid 1H); 4.69-4.61 (septet, J = 6.15 Hz,methylamide 1H); 3.95-3.89 (m, 2H); 3.46 (d, J = 11.43 Hz, 2H); 2.98 (d,J = 4.84 Hz, 3H); 2.37 (T, J = 10.55 Hz, 2H); 1.37 (d, J = 6.15 Hz, 6H);1.25 (d, J = 6.15 Hz, 6H) 139. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃:(M + H)⁺ = 396 B >30 isopropoxy-6-(1H- 8.547 (s, 1H); 7.89-7.84 (m, 2H);tetrazol-5-yl)- 7.61 (s, 1H); 7.60-7.20 (m, 2H); benzofuran-3- 5.8 (brs,1H); 5.0-4.92 (m, 1H); carboxylic acid 3.26 (brs, 1H); 2.99 (d, J = 5.1Hz, methylamide 3H); 1.52 (d, J = 6.0 Hz, 6H) 140.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 427 B <10(4-hydroxy-piperidin-1- 8.28 (d, J = 4.84 Hz, 1H); yl)-5-isopropoxy-7.92-7.86 (m, 2H); 7.33 (t, J = 8.79 Hz, benzofuran-3- 2H); 7.16 (s,1H); 7.03 (s, 1H); carboxylic acid 4.64-4.56 (m, 2H); 3.61 (m, 1H);methylamide 3.35 (m, 2H); 2.82 (d, J = 4.40 Hz, 3H); 2.74-2.67 (m, 2H);1.88-1.85 (m, 2H); 1.62-1.52 (m, 2H); 1.29 (d, J = 5.72 Hz, 6H) 141.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 427 B <10(3-hydroxy-piperidin-1- 8.29 (d, J = 4.84 Hz, 1H); yl)-5-isopropoxy-7.92-7.87 (m, 2H); 7.33 (t, J = 8.79 Hz, benzofuran-3- 2H); 7.14 (s,1H); 7.03 (s, 1H); carboxylic acid 4.73 (d, J = 4.84 Hz, 1H);methylamide 4.63-4.55 (septet, J = 6.15 Hz, 1H); 3.67-3.65 (m, 1H); 3.49(d, J = 8.79 Hz, 2H); 2.82 (d, J = 4.40 Hz, 3H); 2.5 (m, 1H); 2.33 (t, J= 9.67 Hz, 1H); 1.95-1.91 (m, 1H); 1.74 (m, 1H); 1.62-1.58 (m, 2H); 1.29(d, J = 6.15 Hz, 3H); 1.28 (d, J = 5.71, 3H) 142. 2-(4-Fluoro-phenyl)-5-¹H NMR in DMSO: (M + H)⁺ = 477 A <10 isopropoxy-6- 8.48-8.47 (d, J =4.69 Hz, 1H); (morpholine-4- 8.01 (s, 1H); 8.00-7.95 (m, 2H);sulfonyl)-benzofuran-3- 7.44-7.38 (t, J = 8.79 Hz, 2H); carboxylic acid7.34 (s, 1H); 4.91-4.83 (septet, methylamide J = 5.86 Hz, 1H); 3.62-3.59(m, 4H); 3.16-3.13 (m, 4H); 2.85-2.84 (d, J = 4.69 Hz, 3H); 1.37-1.35(d, J = 5.86 Hz, 6H) 143. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M +H)⁺ = 421 A >30 isopropoxy-6- 8.46-8.45 (d, J = 4.10 Hz, 1H);methylsulfamoyl- 7.99-7.95 (m, 2H); 7.95 (s, 1H); benzofuran-3-7.43-7.37 (t, J = 8.79 Hz, 2H); carboxylic acid 7.32 (s, 1H); 6.64 (d, J= 4.69 Hz, methylamide 1H); 4.90-4.82 (septet, J = 5.86 Hz, 1H);2.85-2.83 (d, J = 4.69 Hz, 3H); 2.48-2.46 (d, J = 4.69 Hz, 3H);1.38-1.36 (d, J = 5.86 Hz, 6H) 144. 6-Dimethylsulfamoyl-2- ¹H NMR inDMSO: (M + H)⁺ = 435 A <30 (4-fluoro-phenyl)-5- 8.461 = 8.451 (d, J =4.689 Hz, 1H); isopropoxy-benzofuran- 8.016-7.949 (m, 3H); 3-carboxylicacid 7.436-7.377 (t, J = 8.791 Hz, 2H); methylamide 7.323 (s, 1H);4.904-4.823 (septet, J = 5.861 Hz, 1H); 2.848-2.832 (d, J = 4.689 Hz,3H); 2.775 (s, 6H); 1.365-1.344 (d, J = 6.447 Hz, 6H) 145.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 449 B <10isopropoxy-6-(propane- 8.85 (s, 1H); 8.36 (m, 1H); 2-sulfonylamino)-7.91 (dd, J = 9.2, 5.3 Hz, 2H); 7.59 (s, benzofuran-3- 1H); 7.36 (t, J =8.8 Hz, 2H); carboxylic acid 7.13 (s, 1H); 4.75 (heptuplet, methylamideJ = 5.6 Hz, 1H); 3.21 (heptuplet, J = 5.5 Hz, 1H); 2.82 (d, J = 4.9 Hz,3H); 1.36 (d, J = 5.5 Hz, 6H); 1.28 (d, J = 5.6 Hz, 6H) 146.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 371 B >30isopropoxy-benzofuran- 8.33 (s, 1H); 8.10 (brs, 1H); 3,6-dicarboxylicacid 6- 7.88-7.84 (m, 2H); 7.48 (s, 1H); amide 3-methylamide 7.25-7.18(m, 2H); 5.88 (brs, 1H); 5.75 (brs, 1H); 4.88-4.80 (m, 1H); 2.99 (d, J =5.4 Hz, 3H); 1.46 (d, J = 6.3 Hz, 6H) 147. 2-(4-Fluoro-phenyl)-5- ¹H NMRin DMSO: (M + H)⁺ = 406 A <10 isopropoxy-6- 9.13 (s, 1H); 8.99 (s, 2H);pyrimidin-5-yl- 8.41 (q, br, 1H); 7.92 (m, 2H); benzofuran-3- 7.82 (s,1H); 7.36 (m, 2H); 7.27 (s, carboxylic acid 1H); 4.64 (m, 1H); 2.83 (d,3H); methylamide 1.23 (d, 6H) 148. 6-tert-Butylamino-2-(4- ¹H NMR inCDCl₃: (M + H)⁺ = 399 A <10 fluoro-phenyl)-5- 7.85-7.80 (m, 2H); 7.18(s, 1H); isopropoxy-benzofuran- 7.14 (t, J = 8.79 Hz, 2H); 6.98 (s,3-carboxylic acid 1H); 5.74 (brs, 1H); methylamide 4.60-4.52 (septet, J= 6.15 Hz, 1H); 4.57 (s, 1H); 2.97 (d, J = 4.84 Hz, 3H); 1.41 (s, 9H);1.37 (d, J = 6.15 Hz, 6H) 149. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M− H)⁻ = 406.0 C >30 isopropoxy-6- 8.39-8.37 (d, J = 4.69 Hz, 1H);sulfamoyl-benzofuran- 7.97-7.93 (m, 2H); 7.91 (s, 1H); 3-carboxylic acid7.39-7.33 (t, J = 8.79 Hz, 2H); methylamide 7.07 (s, 1H); 4.66 (septet,J = 6.45 Hz, 1H); 2.84-2.82 (d, J = 4.69 Hz, 3H); 1.30-1.28 (d, J = 6.45Hz, 6H) 150. 6-Cyclobutylsulfamoyl- ¹H NMR in CDCl₃: (M + H)⁺ = 461.0 B<30 2-(4-fluoro-phenyl)-5- 8.057 (s, 1H); 7.869-7.823 (m,isopropoxy-benzofuran- 2H); 7.522 (s, 1H); 3-carboxylic acid 7.248-7.205(m, 2H); 5.766 (brs, 1H); methylamide 5.156-5.125 (d, J = 9.377 Hz, 1H);4.895-4.813 (septet, J = 5.862 Hz, 1H); 3.787-3.707 (sextet, J = 8.206Hz, 1H); 2.984-2.969 (d, J = 4.689 Hz, 3H); 2.063-1.967 (m, 2H);1.828-1.734 (m, 2H); 1.580-1.512 (m, 2H); 1.494-1.475 (d, J = 5.862 Hz,6H) 151. 2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ = 394 A <30furan-2-yl-5- 7.96 (s, 1H); 7.88 (m, 2H); isopropoxy-benzofuran- 7.48(d, 1H); 7.37 (s, 1H); 7.17 (m, 3-carboxylic acid 2H); 7.08 (d, 1H);6.51 (d, 1H); methylamide 5.75 (s, br, 1H); 4.79 (m, 1H); 2.99 (d, 3H);1.45 (d, 6H) 152. 2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ = 394A <10 furan-3-yl-5- 8.12 (s, 1H); 7.90 (m, 2H); isopropoxy-benzofuran-7.61 (s, 1H); 7.48 (d, 1H); 7.38 (s, 3-carboxylic acid 1H); 7.18 (m,2H); 6.83 (d, 1H); methylamide 5.75 (s, br, 1H); 4.79 (m, 1H); 2.99 (d,3H); 1.45 (d, 6H) 153. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺= 405 A <10 isopropoxy-6-pyridin-3- 8.80 (d, 1H); 8.57 (dd, 2H);yl-benzofuran-3- 7.92 (m, 3H); 7.45 (s, 2H); 7.33 (dd, carboxylic acid1H); 7.20 (m, 2H); 5.80 (s, br, methylamide 1H); 4.56 (m, 1H); 2.99 (d,3H); 1.28 (d, 6H) 154. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ =461.0 A <10 isopropoxy-6- 8.455-8.471 (m, 1H); 8.028 (s, (pyrrolidine-1-1H), 7.996-7.949 (m, 2H); sulfonyl)-benzofuran-3- 7.436-7.375 (m, 2H);7.321 (s, carboxylic acid 1H); 4.918-4.838 (septet, methylamide J =5.861 Hz, 1H); 2.846-2.832 (d, J = 4.103, 3H); 2.512-2.486 (pentet, J =1.758 Hz, 4H); 1.779-1.736 (t, J = 6.447 Hz, 4H); 1.371-1.350 (d, J =6.447 Hz, 6H) 155. 6- ¹H NMR in DMSO: (M + H)⁺ = 447.0 A <10Cyclopropylsulfamoyl- 8.47-8.46 (d, J = 41.0 Hz, 1H);2-(4-fluoro-phenyl)-5- 8.03 (s, 1H); 8.00-7.94 (m, 2H);isopropoxy-benzofuran- 7.44-7.38 (t, J = 8.79 Hz, 2H); 3-carboxylic acid7.32 (s, 1H); 7.21 (s, 1H); methylamide 4.89-4.85 (septet, J = 5.86 Hz,1H); 2.85-2.83 (d, J = 4.69 Hz, 3H); 2.17 (m, 1H); 1.38-1.36 (d, J =5.86 Hz, 6H); 0.44 (m, 4H) 156. 6-Ethylsulfamoyl-2-(4- ¹H NMR in DMSO:(M + H)⁺ = 435 A <10 fluoro-phenyl)-5- 8.87 (s, 1H); 8.36 (m, 1H);isopropoxy-benzofuran- 7.91 (dd, J = 9.0, 5.3 Hz, 2H); 7.56 (s,3-carboxylic acid 1H); 7.36 (t, J = 8.8 Hz, 2H); methylamide 7.14 (s,1H); 4.75 (heptuplet, J = 6.1 Hz, 1H); 3.05 (quadruplet, J = 7.5 Hz,2H); 2.82 (d, J = 4.8 Hz, 3H); 1.33 (d, J = 6.1 Hz, 6H); 1.26 (t, J =7.5 Hz, 3H) 157. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 354 A<10 isopropoxy-6-vinyl- 8.39 (q, br, 1H); 7.91 (dd, 2H); benzofuran-3-7.82 (s, 1H); 7.35 (dd, 2H); carboxylic acid 7.12 (s, 1H); 7.05 (dd,1H); 6.89 (d, methylamide 1H); 5.27 (d, 1H); 4.60 (m, 1H); 2.81 (d, 3H);1.31 (d, 6H) 158. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 358A <10 isopropoxy-6-methoxy- 7.86 (m, 2H); 7.34 (s, 1H); benzofuran-3-7.16 (t, J = 8.79 Hz, 2H); 7.05 (s, 1H); carboxylic acid 5.75 (brs, 1H);4.55 (m, 1H); methylamide 3.91 (s, 3H); 2.99 (d, J = 4.69 Hz, 3H); 1.39(d, J = 5.86 Hz, 6H) 159. 6-(3,5-Dimethyl- ¹H NMR in CDCl₃: (M + H)⁺ =423 A <1 isoxazol-4-yl)-2-(4- 7.90-7.85 (m, 2H); 7.63 (s, 2H);fluoro-phenyl)-5- 7.23-7.17 (m, 3H); 5.78 (brs, isopropoxy-benzofuran-1H); 4.52-4.48 (m, 1H); 3.0 (d, 3-carboxylic acid J = 4.8 Hz, 3H); 2.32(s, 3H); methylamide 2.20 (s, 3H); 1.24 (d, J = 6.3 Hz, 6H) 160.2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ = 355.9 A <30formyl-5-isopropoxy- 10.524 (s, 1H); 7.93 (s, 1H); benzofuran-3-7.90-7.85 (m, 2H); 7.44 (s, 1H); carboxylic acid 7.25-7.19 (m, 2H); 5.78(br, 1H); methylamide 4.76 (pent, 1H); 2.98 (d, 3H); 1.43 (d, 6H) 161.2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ = 423 A <10(6-fluoro-pyridin-3-yl)- 8.52 (s, 1H); 8.45 (d, 1H); 5-isopropoxy- 7.88(dd, 2H); 7.45 (s, 1H); 7.38 (m, benzofuran-3- 1H); 7.26 (s, 1H); 7.20(dd, 2H); carboxylic acid 5.77 (s, br, 1H); 4.55 (m, 1H); methylamide2.99 (d, 3H); 1.24 (d, 6H) 162. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃:(M + H)⁺ = 435 B <10 isopropoxy-6- 7.85-7.81 (m, 2H); 7.44 (s, 1H);(methanesulfonylamino- 7.41 (s, 1H), 7.23-7.17 (m, 2H),methyl)-benzofuran-3- 5.73 (s, 1H); 4.98 (t, J = 5.4 Hz, carboxylic acid1H); 4.78-4.71 (m, 1H); 4.39 (d, methylamide J = 6.6 Hz, 3H); 2.97 (d, J= 4.8 Hz, 3H); 2.74 (s, 3H); 1.40 (d, J = 5.7 Hz, 6H) 163.6-(Cyclopentyl- ¹H NMR in DMSO: (M + H)⁺ = 489 A <1 methanesulfonyl-8.42 (m, 1H); 7.94 (dd, J = 6.2 & amino)-2-(4-fluoro- 8.8 Hz, 2H); 7.53(s, 1H); 7.38 (t, phenyl)-5-isopropoxy- J = 8.8 Hz, 2H); 7.13 (s, 1H);benzofuran-3- 4.76 (heptuplet, J = 5.7 Hz, 1H); carboxylic acid 4.28(quintuplet, J = 8.8 Hz, 1H); methylamide 3.11 (s, 3H); 2.83 (m, 3H);1.93 (m, 2H); 1.45 (m, 2H); 1.34 (m, 4H) 164. 2-(4-Fluoro-phenyl)-6- ¹HNMR in DMSO: (M + H)⁺ = 465 A <10 [(2-hydroxy-ethyl)- 8.41 (m, 1H); 7.93(dd, J = 5.2 Hz, methanesulfonyl- 2H); 7.60 (s, 1H); 7.38 (t,amino]-5-isopropoxy- J = 8.8 Hz, 2H); 7.16 (s, 1H); benzofuran-3- 4.78(heptuplet, J = 5.8 Hz, 1H); carboxylic acid 4.67 (t, J = 5.7 Hz, 1H);3.60 (brs, 1H); methylamide 3.04 (s, 3H); 2.83 (d, J = 4.8 Hz, 3H); 1.34(d, J = 5.7 Hz, 6H) 165. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M +H)⁺ = 316 C >30 hydroxy-6-methoxy- 7.94 (m, 2H); 7.28 (s, 1H);benzofuran-3- 7.15 (t, 2H, J = 8.79 Hz); 7.04 (s, 1H); carboxylic acid5.82 (brs, 1H); 5.59 (s, 1H); methylamide 3.97 (s, 3H); 3.01 (d, 3H, J =5.28 Hz) 166. 5-Ethoxy-2-(4-fluoro- ¹H NMR in DMSO: (M + H)⁺ = 399 B <10phenyl)-6-morpholin-4- 8.30 (m, 1H); 7.88 (m, 2H); yl-benzofuran-3- 7.32(t, 2H, J = 8.79 Hz); 7.16 (s, 1H); carboxylic acid 7.04 (s, 1H); 4.06(q, 2H, J = 7.03 Hz); methylamide 3.74 (brm, 4H); 3.02 (brm, 4H); 2.80(d, 3H, J = 4.69 Hz); 1.36 (t, 3H, J = 7.03 Hz) 167.5-(4-Fluoro-benzyloxy)- ¹H NMR in DMSO: (M + H)⁺ = 479 B <12-(4-fluoro-phenyl)-6- 8.30 (m, 1H); 7.88 (m, 2H); morpholin-4-yl- 7.55(m, 2H); 7.33 (t, 2H, J = 8.79 Hz); benzofuran-3- 7.27-7.20 (m, 4H);5.14 (s, 2H); carboxylic acid 3.72 (brm, 4H); 3.03 (brm, 4H);methylamide 2.82 (d, 3H, J = 4.69) 168. 2-(4-Fluoro-phenyl)-5- ¹H NMR inCDCl₃: (M + H)⁺ = 395 A <10 isopropoxy-6-oxazol-5- 7.91-7.83 (m, 4H);7.69 (s, 1H); yl-benzofuran-3- 7.41 (s, 1H); 7.22-7.14 (m, 2H);carboxylic acid 5.79 (brs, 1H); 4.86-4.78 (m, methylamide 1H); 2.99 (d,J = 4.8 Hz, 2H); 1.46 (d, J = 6.3 Hz, 6H) 169. 2-(4-Fluoro-phenyl)-6- ¹HNMR in DMSO: (M + H)⁺ = 491 A <1 (4-hydroxy-piperidine- 8.47-8.49 (d,1H, J = 4.69 Hz); 1-sulfonyl)-5- 8.01 (s, 1H); 7.95-8.00 (m, 2H);isopropoxy-benzofuran- 7.38-7.44 (t, 2H, J = 8.79 Hz); 3-carboxylic acid7.32 (s, 1H); 4.82-4.90 (septet, methylamide 1H, J = 5.86 Hz); 4.67-4.69(d, 1H, J = 4.10 Hz); 3.58-3.59 (m, 1H); 3.35-3.45 (m, 2H); 3.24-3.30(m, 1H); 2.92-3.00 (m, 2H); 2.84-2.85 (d, 3H, J = 4.69 Hz); 1.69-1.73(m, 2H); 1.36-1.41 (m, 1H); 1.34-1.36 (d, 6H, J = 5.86 Hz) 170.6-(4,4-Difluoro- ¹H NMR in CDCl₃: (M + H)⁺ = 447 C <1piperidin-1-yl)-2-(4- 7.87 (m, 2H); 7.31 (s, 1H); fluoro-phenyl)-5- 7.17(t, J = 8.35 Hz, 2H); 7.07 (s, 1H); isopropoxy-benzofuran- 5.74 (s, 1H);4.69-4.61 (septet, 3-carboxylic acid J = 6.16 Hz, 1H); 3.23-3.19 (m,methylamide 4H); 2.98 (d, J = 5.27 Hz, 3H); 2.24-2.11 (m, 4H); 1.39 (d,J = 6.16 Hz, 6H) 171. 2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ =429 B <1 (4-fluoro-piperidin-1- 7.89-7.83 (m, 2H); 7.28 (s, 1H);yl)-5-isopropoxy- 7.16 (t, J = 8.79 Hz, 2H); 7.07 (s, benzofuran-3- 1H);5.76 (s, 1H); 4.92-4.72 (m, carboxylic acid 1H); 4.69-4.61 (septet, J =6.16 Hz, methylamide 1H); 3.24-3.22 (m, 2H); 3.08-3.01 (m, 2H); 2.98 (d,J = 4.84 Hz, 3H); 2.18-2.02 (m, 4H); 1.38 (d, J = 5.71 Hz, 6H) 172.5-Difluoromethoxy-2- ¹H NMR in CDCl₃: (M + H)⁺ = 421 A <1(4-fluoro-phenyl)-6- 7.87 (dd, J = 8.8, 5.7 Hz, 2H); morpholin-4-yl-7.54 (s, 1H); 7.16 (t, J = 8.8 Hz, 2H); benzofuran-3- 7.11 (s, 1H); 6.57(t, J = 75.6 Hz, carboxylic acid 1H); 5.92 (d, J = 4.7 Hz, 1H);methylamide 3.87 (t, J = 4.0 Hz, 4H); 3.08 (t, J = 4.0 Hz, 4H); 2.98 (d,J = 4.9 Hz, 3H) 173. 5-Cyclopentyloxy-2-(4- ¹H NMR in CDCl₃: (M − H)⁻ =437 A <1 fluoro-phenyl)-6- 7.86 (dd, J = 9.4, 5.3 Hz, 2H);morpholin-4-yl- 7.28 (s, 1H); 7.16 (t, J = 9.4 Hz, 2H); benzofuran-3-7.04 (s, 1H); 5.74 (brs, 1H); carboxylic acid 4.90 (m, 1H); 3.90 (t, J =4.7 Hz, 4H); methylamide 3.11 (t, J = 4.7 Hz, 1H); 2.98 (d, J = 4.7 Hz,3H); 1.95 (m, 4H); 1.80 (m, 2H); 1.70 (m, 2H) 174.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 379 B <30 hydroxy-6-8.36 (d, J = 14.7 Hz, 1H); 7.91 (dd, methanesulfonylamino- J = 8.8, 3.0Hz, 2H); 7.48 (s, 1H); benzofuran-3- 7.36 (t, J = 8.8 Hz, 2H); 7.08 (s,carboxylic acid 1H); 2.98 (s, 1H); 2.82 (d, methylamide J = 4.7 Hz, 3H)175. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 493 A <1isopropoxy-6- 8.47-8.48 (d, 1H J+4.10 Hz); (thiomorpholine-4- 8.03 (s1H); 7.95-8.00 (m, 2H); sulfonyl)-benzofuran-3- 7.38-7.44 (t, 2H, J =8.79 Hz); carboxylic acid 7.33 (s, 1H); 4.84-4.92 (septet, methylamide1H, J = 6.45 Hz); 3.42-3.46 (m, 4H); 2.83-2.85 (d, 3H, J = 4.69 Hz);2.62-2.65 (m, 4H); 1.35-1.37 (d, 6H, J = 5.86 Hz) 176.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 477 A <1(3-hydroxy-pyrrolidine- 8.46-8.48 (d, 1H, J = 4.69 Hz); 1-sulfonyl)-5-8.03 (s, 1H); 7.95-7.99 (m, 2H); isopropoxy-benzofuran- 7.38-7.43 (t,2H, J = 8.79 Hz); 3-carboxylic acid 7.31 (s, 1H); 4.99 (br.s, 1H);methylamide 4.82-4.80 (septet, 1H, J = 5.86 Hz); 4.24 (br.s, 1H);3.38-3.46 (m, 4H); 3.07-3.11 (dd, 1H, J = 2.35 Hz, 9.96 Hz); 2.83-2.84(d, 3H, J = 4.69 Hz); 1.79-1.86 (m, 1H); 1.68-1.77 (m, 1H); 1.35-1.37(d, 6H, J = 5.86 Hz) 177. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M +H)⁺ = 405 A <10 isopropoxy-6-pyridin-4- 8.61 (m, 2H); 8.42 (s, 1H);yl-benzofuran-3- 7.94 (dd, 2H); 7.72 (s, 1H); 7.60 (d, carboxylic acid2H); 7.36 (dd, 2H); 7.25 (s, 1H); methylamide 4.6 (m, 1H); 2.84 (d, 3H);1.22 (d, 6H) 178. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 482A <10 isopropoxy-6-(3- 8.42 (m, 1H); 8.16 (m, 1H); methanesulfonyl-7.98-7.88 (m, 4H); 7.72 (s, 1H); phenyl)-benzofuran-3- 7.69 (t, 1H);7.39 (dd, 2H); carboxylic acid 7.27 (s, 1H); 4.60 (m, 1H); 3.26 (s,methylamide 3H); 2.86 (d, 3H); 1.29 (d, 6H) 179. 2-(4-Fluoro-phenyl)-5-¹H NMR in DMSO: (M + H)⁺ = 482 A <10 isopropoxy-6-(4- 8.43 (m, 1H);7.99-7.94 (m, 4H); methanesulfonyl- 7.84 (d, 2H); 7.70 (s, 1H);phenyl)-benzofuran-3- 7.41 (dd, 2H); 7.27 (s, 1H); 4.62 (m, carboxylicacid 1H); 3.28 (s, 3H); 2.85 (d, 3H); methylamide 1.24 (d, 6H) 180.5-(2-Chloro-ethoxy)-2- ¹H NMR in CDCl₃: (M + H)⁺ = 433 A >30(4-fluoro-phenyl)-6- 7.85-7.80 (m, 2H); 7.32 (s, 1H); morpholin-4-yl-7.20-7.15 (m, 2H); 7.08 (s, 2H); benzofuran-3- 5.75 (brs, 2H); 4.37-4.33(m, carboxylic acid 2H); 4.94-4.89 (m, 6H); methylamide 3.17-3.14 (m,4H); 2.97 (d, J = 5.4 Hz, 3H) 181. 6-Benzyloxy-2-(4- ¹H NMR in DMSO:(M + H)⁺ = 406 A <10 fluoro-phenyl)-5- 7.80 (dd, J = 8.8, 5.3 Hz, 2H);methoxy-benzofuran-3- 7.50 (m, 2H); 7.40 (m, 3H); 7.34 (s, carboxylicacid 1H); 7.16 (t, J = 8.8 Hz, 2H); methylamide 7.05 (s, 1H); 5.75 (brd, J = 4.7 Hz, 1H); 5.22 (s, 1H); 3.96 (s, 3H); 2.99 (d, J = 4.7 Hz, 3H)182. 6-Amino-2-(4-fluoro- ¹H NMR in DMSO: (M + H)⁺ = 301 B <30phenyl)-5-hydroxy- 10.55 (br s, 1H); 8.40 (d, benzofuran-3- J = 4.7 Hz,1H); 7.90 (dd, J = 8.8, carboxylic acid 5.3 Hz, 2H); 7.61 (s, 1H); 7.34(t, methylamide J = 8.8 Hz, 2H); 7.16 (s, 1H); 2.79 (d, J = 4.7 Hz, 3H)183. 5,6-Bis-benzyloxy-2-(4- ¹H NMR in DMSO: (M + H)⁺ = 482 D <10fluoro-phenyl)- 8.29 (m, 1H); 7.86 (m, 2H); benzofuran-3- 7.49-7.30 (m,13H); 7.23 (s, 1H); carboxylic acid 5.22 (s, 2H); 5.14 (s, 2H); 2.80 (d,methylamide 3H, J = 4.10) 184. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃:(M + H)⁺ = 464 B <30 isopropoxy-6-(5- 8.17 (s, 1H); 7.91-7.86 (m, 2H);trifluoromethyl- 7.54 (s, 1H); 7.25-7.19 (m, 2H);[1,2,4]oxadiazol-3-yl)- 5.77 (brs, 1H); 4.81-4.73 (m, benzofuran-3- 1H);3.0 (d, J = 4.8 Hz, 3H); carboxylic acid 1.44 (d, J = 6.3 Hz, 6H)methylamide 185. [2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 455C <10 isopropoxy-3- 7.87-7.81 (m, 2H); 7.31 (s, 1H); methylcarbamoyl-7.16 (t, J = 8.35 Hz, 2H); 7.03 (s, benzofuran-6-yl]- 1H); 5.80 (s, 1H);piperazine-1-carboxylic 4.69-4.61 (septet, J = 6.15 Hz, 1H); 4.53 (s,acid amide 2H); 3.60-3.57 (m, 4H); 3.12-3.09 (m, 4H); 2.98 (d, J = 5.27Hz, 3H); 1.38 (d, J = 6.15 Hz, 6H) 186. 2-(4-Fluoro-phenyl)-5- ¹H NMR inCDCl₃: (M + H)⁺ = 429 A <1 isopropoxy-6- 7.87-7.83 (m, 2H); 7.29 (s,1H); thiomorpholin-4-yl- 7.16 (t, J = 8.35 Hz, 2H); 7.05 (s,benzofuran-3- 1H); 5.73 (s, 1H); carboxylic acid 4.65-4.62 (septet, J =5.71 Hz, 1H); 3.34 (m, methylamide 4H); 2.98 (d, J = 4.84 Hz, 3H); 2.84(m, 4H); 1.37 (d, J = 6.15 Hz, 6H) 187. 2-(4-Fluoro-phenyl)-5- ¹H NMR inCDCl₃: (M − H)⁻ = 370 C <10 isopropoxy-3- 8.41-8.42 (d, 1H, J = 4.69Hz); methylcarbamoyl- 7.93-7.97 (m, 2H); 7.80 (s, 1H); benzofuran-6-7.35-7.41 (t, 2H, J = 8.79 Hz); carboxylic acid 7.20 (s, 1H); 4.58-4.66(septet, 1H, J = 5.86 Hz); 2.83-2.84 (d, 3H, J = 4.69 Hz); 1.28-1.30 (d,6H, J = 5.86 Hz) 188. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ =445 C <10 isopropoxy-6-(1-oxo- 7.84-7.82 (m, 2H); 7.34 (s, 1H);thiomorpholin-4-yl)- 7.18 (t, J = 8.35, 2H); 7.13 (s, benzofuran-3- 1H);5.76 (s, 1H); carboxylic acid 4.69-4.65 (septet, J = 5.71 Hz, 1H);methylamide 3.75-3.68 (m, 2H); 3.39-3.35 (m, 2H); 3.10 (s, 4H); 2.99 (d,J = 4.40 Hz, 3H); 1.41 (d, J = 6.15 Hz, 6H) 189. {[2-(4-Fluoro-phenyl)-¹H NMR in DMSO: (M + H)⁺ = 479 B <1 5-isopropoxy-3- 10.9 (s, 1H); 8.43(m, 1H); methylcarbamoyl- 7.96 (m, 2H); 7.66 (s, 1H); 7.38 (m,benzofuran-6-yl]- 2H); 7.17 (s, 1H); methanesulfonyl- 4.79 (heptuplet, J= 6.1 Hz, 1H); amino}-acetic acid 4.28 (s, 2H); 3.08 (s, 3H); 2.83 (d, J= 4.8 Hz, 3H); 1.35 (d, J = 6.1 Hz, 6H) 190. 6-(Cyclobutyl- ¹H NMR inDMSO: (M + H)⁺ = 475 A <1 methanesulfonyl- 8.43 (m, 1H); 7.93 (dd, J =3.1 & amino)-2-(4-fluoro- 6.6 Hz, 2H); 7.57 (s, 1H); 7.39 (t,phenyl)-5-isopropoxy- J = 8.8 Hz, 2H); 7.15 (s, 1H); benzofuran-3- 4.78(heptuplet, J = 6.1 Hz, 1H); carboxylic acid 3.2 (m, 1H); 3.02 (s, 3H);2.83 (d, methylamide J = 5.8 Hz, 3H); 2.46 (m, 6H); 2.38 (d, 6.1 Hz, 6H)191. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 534 A <1isopropoxy-6- 8.42 (d, J = 4.7 Hz, 1H); 7.93 (dd, [methanesulfonyl-(2- J= 7.0 & 9.4 Hz, 2H); 7.58 (s, morpholin-4-yl-ethyl)- 1H); 7.38 (t, J =8.8 Hz, 2H); amino]-benzofuran-3- 7.16 (s, 1H); 4.79 (heptuplet, J = 5.8Hz, carboxylic acid 1H); 3.50 (t, J = 4.6 Hz, methylamide 4H); 3.16 (m,2H); 3.06 (s, 3H); 2.83 (d, J = 4.6 Hz, 3H) 192. 2-(4-Fluoro-phenyl)- ¹HNMR in DMSO: (M + H)⁺ = 302 C >30 5,6-dihydroxy- 8.25 (brs, 1H); 7.83(m, 2H); benzofuran-3- 7.28 (m, 2H); 6.96 (d, 1H, carboxylic acid J =2.34 Hz); 6.90 (d, 1H, J = 2.34 Hz); methylamide 2.77 (brd, 3H, J = 6.45Hz) 193. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 479 A <1isopropoxy-6- 8.48 (m, 1H); 7.95 (dd, J = 5.2 & [methanesulfonyl-(2- 8.7Hz, 2H); 7.53 (s, 1H); methoxy-ethyl)-amino]- 7.39 (t, J = 8.8 Hz, 2H);7.17 (s, 1H); benzofuran-3- 4.79 (heptuplet, J = 5.9 Hz, 1H); carboxylicacid 3.34 (m, 6H); 3.18 (s 3H); methylamide 3.05 (s, 3H); 2.83 (d, J =4.7 Hz, 3H); 1.34 (d, J = 5.8 Hz, 6H) 194. 6-Benzyloxy-2-(4- ¹H NMR inCDCl₃: (M + H)⁺ = 434 B *** fluoro-phenyl)-5- 7.85 (m, 2H); 7.47 (m,2H); isopropoxy-benzofuran- 7.41-7.31 (m, 4H); 7.15 (t, 2H, 3-carboxylicacid J = 8.79 Hz); 7.08 (s, 1H); methylamide 5.75 (brs, 1H); 5.17 (s,2H); 4.55 (m, 1H); 2.99 (d, 3H, J = 5.28 Hz); 1.38 (d, 6H, J = 6.45 Hz)195. 6-(Allyl- ¹H NMR in DMSO: (M + H)⁺ = 461 A <1 methanesulfonyl- 8.41(m, 1H); 7.93 (dd, J = 5.3 & amino)-2-(4-fluoro- 8.8 Hz, 2H); 7.38 (s,1H); 7.34 (t, phenyl)-5-isopropoxy- J = 8.8 Hz, 2H); 5.81 (m, 1H);benzofuran-3- 5.10 (dd, J = 1.8 & 17 Hz, 1H); carboxylic acid 5.02 (dd,J = 1.1 & 10 Hz, 1H); methylamide 4.79 (heptuplet, J = 6.4 Hz, 1H); 4.22(m, 2H); 3.06 (s, 3H); 2.82 (d, J = 4.7 Hz, 3H) 196.6-Acetyl-2-(4-fluoro- ¹H NMR in CDCl₃: (M + H)⁺ = 370.0 A <1phenyl)-5-isopropoxy- 7.88 (s, 1H); 7.86 (m, 2H); benzofuran-3- 7.41 (s,1H); 7.18 (m, 2H); 5.77 (brs, carboxylic acid 1H); 4.79 (m, 1H); 3.00(d, methylamide J = 4.8 Hz, 3H); 2.69 (s, 3H); 1.44 (d, J = 6.0 Hz, 6H)197. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 449 C <10isopropoxy-6- 7.85-7.80 (m, 2H); 7.74 (s, 1H); methanesulfonylamino-7.43 (s, 1H); 7.19 (t, J = 8.79 Hz, benzofuran-3- 2H); 6.95 (s, 1H);5.53-5.50 (m, carboxylic acid 1H); 4.78-4.70 (septet, J = 6.15 Hz,isopropylamide 1H); 4.38-4.26 (septet, J = 7.03 Hz, 1H); 2.95 (s, 3H);1.40 (d, J = 5.44 Hz, 6H); 1.18 (d, J = 6.49 Hz, 6H) 198.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 410 A <1isopropoxy-6-(5- 8.07 (s, 1H); 7.92-7.87 (m, 1H); methyl- 7.49 (s, 1H);7.23-7.17 (m, 2H); [1,2,4]oxadiazol-3-yl)- 5.80 (brs, 1H); 4.70-4.64 (s,1H); benzofuran-3- 3.00 (d, J = 4.8 Hz, 3H); 2.65 (s, carboxylic acid3H); 1.41 (d, J = 6.3 Hz, 6H) methylamide 199. 2-(4-Fluoro-phenyl)-5- ¹HNMR in CDCl₃: (M + H)⁺ = 447 A <1 isopropoxy-6- 7.79-7.74 (m, 2H); 7.73(s, 1H); methanesulfonylamino- 7.47 (s, 1H); 7.20 (T, J = 8.79 Hz,benzofuran-3- 2H); 6.95 (s, 1H); 5.8 (s, 1H); carboxylic acid 4.78-4.70(septet, J = 6.15 Hz, cyclopropylamide 1H); 2.95 (s, 3H); 2.90-2.86 (m,1H); 1.40 (d, J = 6.15 Hz, 6H); 0.89-0.82 (m, 2H); 0.53-0.48 (m, 2H)200. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 435 A <1isopropoxy-6- 7.85-7.79 (m, 2H); 7.74 (s, 1H); methanesulfonylamino-7.44 (s, 1H); 7.19 (t, J = 8.35 Hz, benzofuran-3- 2H); 6.95 (s, 1H); 5.7(s, 1H); carboxylic acid 4.80-4.68 (septet, J = 6.15 Hz, ethylamide 1H);3.52-3.43 (m, 2H); 2.95 (s, 3H); 1.39 (d, J = 5.71, 6H); 1.17 (T, J =7.47, 3H) 201. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 482 A<1 (2-methyl-thiazol-4- 7.89 (m, 2H); 7.41 (s, 1H); ylmethoxy)-6- 7.16(m, 3H); 7.10 (s, 1H); 5.78 (brs, morpholin-4-yl- 1H); 5.25 (s, 2H);3.90 (m, 4H); benzofuran-3- 3.16 (m, 4H); 3.00 (d, 3H, carboxylic acid J= 4.69 Hz); 2.74 (s, 3H) methylamide 202. 2-(4-Fluoro-phenyl)-6- ¹H NMRin CDCl₃: (M + H)⁺ = 386.1 A <1 (1-hydroxy-1-methyl- 7.84 (m, 2H); 7.49(s, 1H); ethyl)-5-isopropoxy- 7.39 (s, 1H); 7.19 (m, 2H); 5.73 (brs,benzofuran-3- 1H); 3.56 (m, 1H); 2.99 (d, J = 4.8 Hz, carboxylic acid3H); 1.38 (d, J = 6.1 Hz, 6H) methylamide 203. 5-[5-(3,5-Dimethyl- ¹HNMR in CDCl₃: (M + H)⁺ = 548 B <10 isoxazol-4-yl)- 7.86 (m, 2H); 7.52(s, 1H); [1,2,4]oxadiazol-3- 7.18 (t, 2H, J = 8.79 Hz); 7.12 (s, 1H);ylmethoxy]-2-(4-fluoro- 5.75 (brs, 1H); 5.36 (s, 2H);phenyl)-6-morpholin-4- 3.92 (m, 4H); 3.19 (m, 4H); 2.98 (d,yl-benzofuran-3- 3H, J = 4.69 Hz); 2.81 (s, 3H); carboxylic acid 2.59(s, 3H) methylamide 204. 5-(5-tert-Butyl- ¹H NMR in DMSO: (M + H)⁺ = 509A <1 [1,2,4]oxadiazol-3- 8.28 (br m, 1H); 7.90 (m, 2H);ylmethoxy)-2-(4-fluoro- 7.33 (t, 2H, J = 8.79 Hz); 7.24 (s,phenyl)-6-morpholin-4- 1H); 7.22 (s, 1H); 5.28 (s, 2H); yl-benzofuran-3-3.74 (m, 4H); 3.06 (m, 4H); carboxylic acid 2.81 (d, 3H, J = 4.69); 1.40(s, 9H) methylamide 205. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M +H)⁺ = 396 A <1 isopropoxy-6- 8.75 (s, 1H); 8.14 (s, 1H);[1,2,4]oxadiazol-3-yl- 7.93-7.88 (m, 2H); 7.53 (s, 1H); benzofuran-3-7.24-7.17 (m, 2H); 5.78 (brs, 1H); carboxylic acid 4.70-4.68 (m, 1H);3.0 (d, methylamide J = 4.8 Hz, 3H); 1.42 (d, J = 5.7 Hz, 6H) 206.5-(5-Chloro- ¹H NMR in DMSO: (M + H)⁺ = 504 B <1 [1,2,4]thiadiazol-3-8.38 (brd, 1H, J = 4.69 Hz); ylmethoxy)-2-(4-fluoro- 7.95 (m, 2H); 7.76(s, 1H); 7.58 (s, phenyl)-6-morpholin-4- 1H); 7.38 (t, 2H, J = 8.79 Hz);yl-benzofuran-3- 4.75 (s, 2H); 3.52 (m, 4H); carboxylic acid 2.98 (m,4H); 2.80 (d, 3H, J = 4.69 Hz) methylamide 207. 2-(4-Fluoro-phenyl)-6-¹H NMR in DMSO: (M + H)⁺ = 543 C <10 morpholin-4-yl-5-(5-p- 8.31 (brd,1H, J = 4.69 Hz); tolyl-[1,3,4]oxadiazol- 7.90 (m, 4H); 7.43 (d, 2H, J =7.62 Hz); 2-ylmethoxy)- 7.34 (m, 3H); 7.25 (s, 1H); benzofuran-3- 5.48(s, 2H); 3.69 (m, 4H); carboxylic acid 3.02 (m, 4H); 2.81 (d, 3H, J =4.69 Hz); methylamide 2.40 (s, 3H) 208. 2-(4-Fluoro-phenyl)-6- ¹H NMR inDMSO: (M + H)⁺ = 316 B <30 hydroxy-5-methoxy- 9.33 (s, 1H); 8.28 (d, J =4.4 Hz, benzofuran-3- 1H); 7.85 (dd, J = 8.8, 5.3 Hz, carboxylic acid2H); 7.30 (t, J = 8.8 Hz, 2H); methylamide 7.06 (s, 1H); 7.02 (s, 1H);3.81 (s, 3H); 2.80 (d, J = 4.4 Hz, 3H) 209. 2-(4-Fluoro-phenyl)-5- ¹HNMR in DMSO: (M + H)⁺ = 467 B <10 (1-methyl-1H-tetrazol- 8.31 (d, J =4.4 Hz, 1H); 7.88 (dd, 5-ylmethoxy)-6- J = 8.8, 5.3 Hz, 2H); 7.36 (t,morpholin-4-yl- J = 8.8 Hz, 2H); 7.33 (s, 1H); benzofuran-3- 7.25 (s,1H); 5.54 (s, 2H); 4.14 (s, 3H); carboxylic acid 3.68 (t, J = 4.4 Hz,4H); 2.98 (t, methylamide J = 4.4 Hz, 4H); 2.81 (d, J = 4.4 Hz, 3H))210. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 491 A <1(3-methoxy-benzyloxy)- 8.30 (d, J = 4.4 Hz, 1H); 7.88 (dd,6-morpholin-4-yl- J = 8.8, 5.3 Hz, 2H); 7.32 (m, 3H); benzofuran-3- 7.22(s, 1H); 7.19 (s, 1H); carboxylic acid 7.07 (m, 2H); 6.87 (m, 1H); 5.13(s, methylamide 2H); 3.76 (s, 3H); 3.73 (brs, 4H); 3.05 (brs, 4H); 2.81(d, J = 4.4 Hz, 3H) 211. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺= 412 A <1 methoxy-6-(1-methyl- 8.32 (d, J = 4.4 Hz, 1H); 7.87 (dd,1H-tetrazol-5- J = 8.3, 5.7 Hz, 2H); 7.55 (s, 1H);ylmethoxy)-benzofuran- 7.33 (t, J = 8.8 Hz, 2H); 7.11 (s, 3-carboxylicacid 1H); 5.56 (s, 2H); 4.15 (s, 3H); methylamide 3.81 (s, 3H); 2.80 (d,J = 4.4 Hz, 3H)) 212. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ =493 A <1 [1-(4-fluoro-phenyl)- 7.86 (dd, J = 8.8, 5.3 Hz, 2H);ethoxy]-6-morpholin-4- 7.38 (dd, J = 8.8, 5.3 Hz, 2H); 7.12 (t,yl-benzofuran-3- J = 8.8 Hz, 2H); 7.03 (t, J = 8.8 Hz, carboxylic acid2H); 5.62 (d, J = 4.9 Hz, 1H); methylamide 5.37 (q, J = 6.1 Hz, 1H);3.88 (m, 4H); 3.14 (m, 4H); 2.92 (d, J = 4.9 Hz, 3H); 1.65 (d, J = 6.1Hz, 3H) 213. 5-(4-Cyano-benzyloxy)- ¹H NMR in DMSO: (M + H)⁺ = 486 B <102-(4-fluoro-phenyl)-6- 8.28 (d, J = 4.4 Hz, 1H); 7.88 (m,morpholin-4-yl- 4H); 7.70 (d, J = 8.0 Hz, 2H); benzofuran-3- 7.33 (t, J= 8.8 Hz, 2H); 7.24 (s, carboxylic acid 1H); 7.20 (s, 1H); 5.27 (s, 1H);methylamide 3.74 (m, 4H); 3.04 (m, 4H); 2.81 (d, J = 4.4 Hz, 3H) 214.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 559 B <1[5-(4-methoxy-phenyl)- 8.35 (d, J = 4.4 Hz, 1H); 7.92 (m,[1,2,4]oxadiazol-3- 4H); 7.37 (m, 3H); 7.25 (s, 1H); ylmethoxy]-6- 7.17(d, J = 8.8 Hz, 2H); 5.47 (s, morpholin-4-yl- 2H); 3.84 (s, 3H); 3.69(s, 4H); benzofuran-3- 3.02 (s, 4H); 2.80 (d, J = 4.4 Hz, carboxylicacid 3H) methylamide 215. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M +H)⁺ = 427 B <10 morpholin-4-yl-5-(2- 8.26 (d, J = 4.4 Hz, 1H); 7.87 (dd,oxo-propoxy)- J = 8.3, 5.7 Hz, 2H); 7.32 (t, benzofuran-3- J = 8.8 Hz,2H); 7.20 (s, 1H); carboxylic acid 7.00 (s, 1H); 4.80 (s, 2H); 3.76 (t,methylamide J = 4.7 Hz, 4H); 3.06 (t, J = 4.7 Hz, 4H); 2.80 (d, J = 4.8Hz, 3H); 2.21 (s, 3H) 216. 5-(1-Benzyl-1H- ¹H NMR in DMSO: (M + H)⁺ =541 A <1 imidazol-2-ylmethoxy)- 8.26 (brd, 1H, J = 4.69 Hz);2-(4-fluoro-phenyl)-6- 7.90 (m, 2H); 7.35-7.16 (m, 10H); morpholin-4-yl-6.94 (m, 1H); 5.37 (s, 2H); benzofuran-3- 5.17 (s, 2H); 3.66 (m, 4H);2.95 (m, carboxylic acid 4H); 2.82 (d, 3H, J = 4.69 Hz) methylamide 217.5-(3,5-Dimethyl- ¹H NMR in DMSO: (M + H)⁺ = 480 B <10isoxazol-4-ylmethoxy)- 8.30 (d, 1H, J = 4.39); 2-(4-fluoro-phenyl)-6-7.82 (m, 2H); 7.33 (t, 2H, J = 8.79); morpholin-4-yl- 7.20 (m, 2H); 5.00(s, 2H); benzofuran-3- 3.69 (m, 4H); 2.98 (m, 4H); 2.82 (d, carboxylicacid 3H, J = 4.39 Hz); 2.39 (s, 3H); methylamide 2.26 (s, 3H) 218.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 466 A <1(5-methyl-isoxazol-3- 8.28 (brd, 1H, J = 4.39 Hz); ylmethoxy)-6- 7.90(m, 2H); 7.33 (t, 2H, J = 8.79); morpholin-4-yl- 7.22 (m, 2H); 6.34 (s,1H); benzofuran-3- 5.18 (s, 2H); 3.73 (m, 4H); 3.03 (m, carboxylic acid4H); 2.82 (d, 3H, J = 4.39 Hz); methylamide 2.42 (s, 3H) 219.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 410.9 A <10isopropoxy-6-thiazol-2- 8.50 (s, 1H); 8.46-8.47 (d, yl-benzofuran-3- J =4.69 Hz, 1H); 7.97-8.02 (m, carboxylic acid 3H); 7.80-7.81 (d, J = 3.5Hz, 1H); methylamide 7.38-7.44 (t, J = 8.79 Hz, 2H); 7.36 (s, 1H);4.97-5.06 (septet, J = 6.45 Hz, 1H); 2.84-2.86 (d, J = 5.27 Hz, 3H);1.47-1.49 (d, J = 5.86 Hz, 6H) 220. 2-(4-Fluoro-phenyl)-5- ¹H NMR inCDCl₃: (M + H)⁺ = 393 A <10 isopropoxy-6-(1H- 7.90-7.86 (m, 2H); 7.77(s, 1H); pyrrol-2-yl)- 7.43 (s, 1H); 7.26-7.17 (m, 3H); benzofuran-3-6.90 (s, 1H); 6.67 (s, 1H); carboxylic acid 6.31 (s, 1H); 5.8 (s, 1H,br); 4.78 (m, methylamide 1H); 3.0 (d, 3H); 1.46 (d, 6H) 221.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 435 A <1 (isopropyl-8.44 (m, 1H); 7.94 (dd, 2H, methanesulfonyl- J = 5.28, 8.8 Hz); 7.556(s, 1H); amino)-5-methoxy- 7.39 (t, J = 8.8 Hz, 2H); benzofuran-3- 7.20(s, 1H); 4.27 (heptuplet, carboxylic acid J = 6.4 Hz, 1H); 3.86 (s, 3H);methylamide 3.09 (s, 3H); 2.84 (d, J = 4.7 Hz, 3H); 1.21 (d, J = 7.1 Hz,3H); 1.01 (d, J = 6.5 Hz, 3H) 222. 2-(4-Fluoro-phenyl)-6- ¹H NMR inCDCl₃: (M + H)⁺ = 372 A <1 (1-hydroxy-ethyl)-5- 7.87-7.83 (m, 2H); 7.50(s, 1H); isopropoxy-benzofuran- 7.34 (s, 1H); 7.21-7.16 (m, 2H);3-carboxylic acid 5.72 (bs, 1H); 5.19-5.13 (m, 1H); methylamide4.78-4.69 (m, 1H); 2.98 (d, J = 5.1 Hz, 3H); 2.78 (d, J = 5.1 Hz, 1H);1.55 (d, J = 6.6 Hz, 3H); 1.41 (dd, J = 3.6 Hz, 6.0 Hz, 6H) 223.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 427 C <10isopropoxy-6- 7.89-7.84 (m, 2H); 7.57 (s, 1H); morpholin-4-ylmethyl-7.31 (s, 1H); 7.20-7.16 (m, 2H); benzofuran-3- 5.74 (brs, 1H); 4.64-4.60(m, carboxylic acid 1H); 3.75-3.72 (m, 4H); 3.64 (s, methylamide 2H);2.98 (d, J = 5.1 Hz, 3H); 2.55-2.52 (m, 4H); 1.36 (d, J = 6.3 Hz, 3H)224. 2-(4-Fluoro-phenyl)-6- 1HNMR CDCl₃: (M + H)⁺ = 358 A <10hydroxymethyl-5- 7.87-7.83 (m, 2H); 7.43 (s, 1H); isopropoxy-benzofuran-7.35 (s, 1H); 7.21-7.15 (m, 2H); 3-carboxylic acid 5.73 (brs, 1H;,4.76-4.68 (m, methylamide 3H); 2.98 (d, J = 5.1 Hz, 3H); 2.52-2.50 (m,1H); 1.40 (d, J = 6.0 Hz, 6H) 225. 2-(4-Fluoro-phenyl)-5- ¹H NMR inDMSO: (M + H)⁺ = 451 A <10 (3H-imidazol-4- 8.27 (brd, 1H, J = 4.39 Hz);ylmethoxy)-6- 7.89 (m, 2H); 7.33 (t, 2H, J = 8.79 Hz); morpholin-4-yl-7.28 (s, 1H); 7.19 (s, 1H); benzofuran-3- 7.15 (brs, 1H); 6.90 (brs,1H); carboxylic acid 5.10 (s, 2H); 3.69 (m, 4H); methylamide 3.02 (m,4H); 2.83 (d, 3H, J = 4.39 Hz) 226. 2-(4-Fluoro-phenyl)-5- ¹H NMR inDMSO: (M + H)⁺ = 429 A <1 (2-methoxy-ethoxy)-6- 8.28 (d, 1H, J = 4.69Hz); morpholin-4-yl- 7.89 (m, 2H); 7.32 (t, 2H, J = 8.79 Hz);benzofuran-3- 7.16 (s, 1H); 7.06 (s, 1H); carboxylic acid 4.13 (m, 2H);3.72 (m, 6H); 3.33 (s, methylamide 3H); 3.04 (m, 4H); 2.81 (d, 3H, J =4.69 Hz) 227. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 411 A <1isopropoxy-6-thiazol-5- 9.07 (s, 1H); 8.53 (s, 1H); yl-benzofuran-3-8.41-8.42 (d, J = 4.69 Hz, 1H); 8.19 (s, carboxylic acid 1H); 7.93-7.98(m, 2H); methylamide 7.36-7.42 (t, J = 8.79 Hz, 2H); 7.28 (s, 1H);4.82-4.90 (septet, J = 5.86 Hz, 1H); 2.84-2.86 (d, J = 4.69 Hz, 3H);1.38-1.40 (d, J = 5.86 Hz, 6H) 228. 5-(4-Chloro-1-methyl- ¹H NMR inCDCl₃: (M + H)⁺ = 499 A <1 1H-pyrazol-3- 7.93 (m, 2H); 7.47 (s, 1H);ylmethoxy)-2-(4-fluoro- 7.39 (s, 1H); 7.17 (t, 2H, J = 8.79 Hz);phenyl)-6-morpholin-4- 7.08 (s, 1H); 5.86 (brs, 1H); yl-benzofuran-3-5.17 (s, 2H); 3.89 (m, 7H); 3.16 (m, carboxylic acid 4H); 3.04 (d, 3H, J= 4.84 Hz) methylamide 229. 5-(Cyano-methyl- ¹H NMR in CDCl₃: (M + H)⁺ =424 A <10 methoxy)-2-(4-fluoro- 7.90 (m, 2H); 7.52 (s, 1H);phenyl)-6-morpholin-4- 7.17 (m, 3H); 5.84 (brs, 1H); 5.17 (q,yl-benzofuran-3- 1H, J = 7.03 Hz); 3.89 (t, 4H, carboxylic acid J = 4.69Hz); 3.20 (m, 2H); methylamide 3.00 (m, 5H); 1.80 (d, 3H, J = 6.45 Hz)230. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 394.1 A <10isopropoxy-6-(2H- 7.87 (m, 2H); 7.80 (s, 1H); pyrazol-3-yl)- 7.62 (d, J= 2.4 Hz, 1H); 7.49 (s, 1H); benzofuran-3- 7.24 (m, 2H); 6.69 (d, J =2.4 Hz, carboxylic acid 1H); 5.77 (brs, 1H); 4.83 (m, methylamide 1H);2.99 (d, J = 5.4 Hz, 3H); 1.48 (d, J = 5.7 Hz, 6H) 231.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 408.1 A <1isopropoxy-6-(2- 7.88 (m, 2H); 7.52 (d, J = 1.8 Hz, methyl-2H-pyrazol-3-1H); 7.45 (s, 1H); 7.39 (s, 1H); yl)-benzofuran-3- 7.22 (m, 2H); 6.26(d, J = 1.8 Hz, carboxylic acid 1H); 5.87 (brs, 1H); 4.48 (m,methylamide 1H); 3.76 (s, 3H); 3.00 (d, J = 4.8 Hz, 3H); 1.23 (d, J =5.7 Hz, 6H) 232. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ =408.1 B <10 isopropoxy-6-(1- 8.10 (s, 1H); 7.87 (m, 2H);methyl-1H-pyrazol-3- 7.37 (d, J = 2.1 Hz, 1H); 7.36 (s, 1H);yl)-benzofuran-3- 7.18 (m, 2H); 6.91 (d, J = 2.1 Hz, carboxylic acid1H); 5.82 (brs, 1H); 4.67 (m, methylamide 1H); 3.96 (s, 3H); 2.99 (d, J= 4.8 Hz, 3H); 1.39 (d, J = 6.0 Hz, 6H) 233. 2-(4-Fluoro-phenyl)-5- ¹HNMR in DMSO: (M + H)⁺ = 409.21 B <30 isopropoxy-6-(3- 8.42 (d, J = 4.8Hz, 1H); 8.03 (s, methyl-isoxazol-5-yl)- 1H); 7.95 (dd, J = 5.7, 5.2,8.8 Hz, benzofuran-3- 2H); 7.37 (apparent triplet, carboxylic acid J =8.8 Hz, 2H); 7.28 (s, 1H); methylamide 6.79 (s, 1H); 4.84 (m, 1H); 2.83(d, J = 4.4 Hz, 3H); 2.30 (s, 3H); 1.38 (d, J = 5.7 Hz, 6H) 234.6-[(5-Chloro- ¹H NMR in CDCl₃: (M + H)⁺ = 553 A <10 [1,2,4]thiadiazol-3-7.81 (m, 2H); 7.69 (s, 1H); ylmethyl)- 7.40 (s, 1H); 7.19 (t, 2H, J =8.79 Hz); methanesulfonyl- 5.69 (brs, 1H); 5.09 (brs, 2H);amino]-2-(4-fluoro- 4.78 (m, 1H); 3.09 (s, 3H); phenyl)-5-isopropoxy-2.95 (d, 3H, J = 4.84 Hz); 1.42 (d, 6H, benzofuran-3- J = 6.15 Hz)carboxylic acid methylamide 235. 6-(3,5-Dimethyl- ¹H NMR in CDCl₃: (M +H)⁺ = 438 C >30 isoxazol-4-ylamino)-2- 7.79-7.74 (m, 2H); 7.32 (s, 1H);(4-fluoro-phenyl)-5- 7.14 (t, J = 8.79 Hz, 2H); 6.43 (s,isopropoxy-benzofuran- 1H); 5.73 (s, 1H); 5.50 (s, 1H); 3-carboxylicacid 4.73-4.67 (septet, J = 6.15 Hz, methylamide 1H); 2.97 (d, J = 5.27,3H); 2.32 (s, 3H); 2.13 (s, 3H); 1.43 (d, J = 6.15 Hz, 6H) 236.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 377 A <1methoxy-6-pyridin-3-yl- 8.75 (s, 1H); 8.55 (s, 1H, br); benzofuran-3-8.43 (d, 1H); 7.98-7.93 (m, 2H); carboxylic acid 7.68 (s, 1H); 7.49-7.35(m, 3H); methylamide 7.26 (s, 1H); 3.84 (s, 3H); 2.84 (d, 3H) 237. 6- ¹HNMR in CDCl₃: (M + H)⁺ = 385 C <30 Dimethylaminomethyl- 7.89-7.84 (m,2H); 7.54 (s, 1H); 2-(4-fluoro-phenyl)-5- 7.31 (s, 1H); 7.21-7.15 (m,2H); isopropoxy-benzofuran- 5.55 (brs, 1H); 4.66-4.60 (m, 3-carboxylicacid 1H); 3.64 (s, 2H); 2.99 (d, methylamide J = 5.1 Hz, 3H); 2.34 (s,6H); 1.37 (d, J = 5.7 Hz, 6H) 238. 2-(4-Fluoro-phenyl)-6- ¹H NMR inCDCl₃: (M + H)⁺ = 400 A <1 (1-hydroxy-2-methyl- 7.89-7.84 (m, 2H); 7.43(s, 1H); propyl)-5-isopropoxy- 7.32 (s, 1H); 7.22-7.16 (m, 2H);benzofuran-3- 5.76 (brs; 1H); 4.74-4.60 (m, carboxylic acid 2H); 2.99(d, J = 4.8 Hz, 3H); methylamide 2.61 (d, J = 6.5 Hz, 1H); 2.14-2.09 (m,1H); 1.40 (dd, J = 11.7, 6.0 Hz, 6H); 1.04 (d, J = 6.6 Hz, 3H); 0.85 (d,J = 6.9 Hz, 3H) 239. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ =394.1 C <10 isopropoxy-6-(1H- 8.10 (s, 2H); 7.87 (m, 2H); pyrazol-4-yl)-7.65 (s, 1H); 7.39 (s, 2H); 7.18 (m, benzofuran-3- 2H); 5.79 (brs, 1H);4.72 (m, carboxylic acid 1H); 3.00 (d, J = 5.1 Hz, 3H); methylamide 1.41(d, J = 6.0 Hz, 6H) 240. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺= 451.1 A <1 [methanesulfonyl-(2- 8.49 (m, 1H); 8.00 (dd, J = 5.1 &methoxy-ethyl)-amino]- 8.8 Hz, 2H); 7.63 (s, 1H); 5-methoxy-benzofuran-7.42 (t, J = 8.8 Hz, 2H); 7.26 (s, 1H); 3-carboxylic acid 3.97 (s, 3H);3.78 (m, 1H); methylamide 3.35 (m, 6H); 3.25 (s, 3H); 3.11 (s, 3H); 2.90(d, J = 3.3 Hz, 3H) 241. 6-(3-Cyclopropyl- ¹H NMR in DMSO: (M + H)⁺ =435 B <10 isoxazol-5-yl)-2-(4- 8.44 (broad quartet, J = 4.4 Hz,fluoro-phenyl)-5- 1H); 8.02 (s, 1H); 7.96 (dd, isopropoxy-benzofuran- J= 5.7, 5.3, 9.2 Hz, 2H); 3-carboxylic acid 7.39 (apparent triplet; J =8.8, 9.2 Hz, methylamide 2H); 7.29 (s, 1H); 6.64 (s, 1H); 4.84 (m, 1H);2.85 (d, J = 4.8 Hz, 3H); 2.08 (m, 1H); 1.39 (d, J = 5.7 Hz, 6H); 1.05(m, 2H); 0.84 (m, 2H) 242. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M +H)⁺ = 439 B 30 isopropoxy-6-(3- 8.45 (broad quartet, J = 4.8 Hz,methoxymethyl- 1H); 8.10 (s, 1H); 7.97 (dd, isoxazol-5-yl)- J = 5.7, 8.8Hz, 2H); 7.40 (t, benzofuran-3- J = 8.8 Hz, 2H); 7.32 (s, 1H);carboxylic acid 6.92 (s, 1H); 4.88 (quintet, J = 6.1 Hz, methylamide1H); 4.55 (s, 2H); 3.29 (s, 3H); 2.85 (d, J = 4.4 Hz, 3H); 1.40 (d, J =6.1 Hz, 6H) 243. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 363 B<10 methanesulfonylamino- 8.37 (m, 1H); 7.93 (dd, J = 5.7 &benzofuran-3- 8.8 Hz, 2H); 7.53 (d, J = 8.8 Hz, carboxylic acid 1H);7.45 (d, J = 1.7 Hz, 1H); methylamide 7.36 (t, J = 8.8 Hz, 2H); 7.14(dd, J = 1.7 & 8.8 Hz, 1H); 4.17 (brs, 1H); 2.96 (s, 3H); 2.82 (d, J =4.8 Hz, 3H) 244. 2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ = 394A <1 (1H-imidazol-2-yl)-5- 10.70 (s, 1H); 8.43 (s, 1H);isopropoxy-benzofuran- 7.86-7.81 (m, 2H); 7.48 (s, 1H); 3-carboxylicacid- 7.21-7.15 (m, 3H); 7.12 (s, 1H); methylamide 5.96 (s, 1H);4.91-4.83 (m, 1H); 2.99 (d, J = 4.8 Hz, 3H); 1.49 (d, J = 6.0 Hz, 6H)245. 6-(2,5-Dimethyl-2H- ¹H NMR in CDCl₃: (M + H)⁺ = 422.1 B <10pyrazol-3-yl)-2-(4- 8.08 (s, 1H); 7.88 (m, 2H); fluoro-phenyl)-5- 7.35(s, 1H); 7.19 (m, 2H); 6.67 (s, isopropoxy-benzofuran- 1H); 5.78 (brs,1H); 4.67 (m, 3-carboxylic acid 1H); 3.84 (s, 3H); 3.00 (d, methylamideJ = 4.8 Hz, 3H); 2.33 (s, 3H); 1.39 (d, J = 6.0 Hz, 6H) 246.6-(3,5-Dimethyl-1H- ¹H NMR in CDCl₃: (M + H)⁺ = 422.1 A <1pyrazol-4-yl)-2-(4- 7.91 (m, 2H); 7.40 (s, 1H); fluoro-phenyl)-5- 7.28(s, 1H); 7.18 (m, 2H); 5.80 (brs, isopropoxy-benzofuran- 1H); 4.36 (m,1H); 3.00 (d, 3-carboxylic acid J = 5.4 Hz, 3H); 2.21 (s, 6H);methylamide 1.20 (d, J = 5.7 Hz, 6H) 247. 2-(4-Fluoro-phenyl)-5- ¹H NMRin CDCl₃: (M + H)⁺ = 408.1 B <10 isopropoxy-6-(5- 7.87 (m, 2H); 7.75 (s,1H); methyl-2H-pyrazol-3- 7.47 (s, 1H); 7.20 (m, 2H); 6.47 (s,yl)-benzofuran-3- 1H); 5.75 (brs, 1H); 4.82 (m, carboxylic acid 1H);2.99 (d, J = 5.1 Hz, 3H); methylamide 2.36 (s, 3H); 1.46 (d, J = 6.0 Hz,6H) 248. 6-(1,5-Dimethyl-1H- ¹H NMR in CDCl₃: (M + H)⁺ = 422.1 B <10pyrazol-3-yl)-2-(4- 7.88 (m, 2H); 7.44 (s, 1H); fluoro-phenyl)-5- 7.38(s, 1H); 7.20 (m, 2H); 6.04 (s, isopropoxy-benzofuran- 1H); 5.68 (brs,1H); 4.44 (m, 3-carboxylic acid 1H); 3.68 (s, 3H); 3.00 (d, methylamideJ = 4.8 Hz, 3H); 2.32 (s, 3H); 1.25 (d, J = 6.3 Hz, 6H) 249.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 449 A <10isopropoxy-6- 7.86-7.83 (m, 2H); 7.58 (s, 1H); [(methanesulfonyl- 7.37(s, 1H); 7.22-7.17 (m, 2H); methyl-amino)-methyl]- 5.75 (s, 1H);4.74-4.66 (m, 1H); benzofuran-3- 4.47 (s, 2H); 2.99 (d, J = 5.1 Hz,carboxylic acid 3H); 2.87 (d, J = 5.7 Hz, 6H); methylamide 1.39 (d, J =6.3 Hz, 6H) 250. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 443B <10 (2-hydroxy-2-methyl- 7.87 (dd, J = 8.8 & 5.3 Hz, 2H);propoxy)-6-morpholin- 7.40 (s, 1H); 7.20 (t, J = 8.8 Hz,4-yl-benzofuran-3- 2H); 7.12 (s, 1H); 5.80 (brs, 1H); carboxylic acid3.98 (s, 2H); 3.92 (t, J = 4.4 Hz, methylamide 4H); 3.10 (t, J = 4.4 Hz,4H); 2.96 (d, J = 4.4 Hz, 3H); 1.35 (s, 6H) 251. 2-(4-Fluoro-phenyl)-5-¹H NMR in CDCl₃: (M + H)⁺ = 457 B <10 (2-hydroxy-2-methyl- 7.86 (dd, J =8.8, 5.3 Hz, 2H); butoxy)-6-morpholin-4- 7.40 (s, 2H); 7.22 (t, J = 8.8Hz, yl-benzofuran-3- 2H); 7.12 (s, 1H); 5.90 (brs, 1H); carboxylic acid4.00 (m, 2H); 3.95 (t, J = 4.4 Hz, methylamide 4H); 3.10 (t, J = 4.4 Hz,4H); 2.95 (d, J = 4.4 Hz, 3H); 2.30 (brs, 1H); 1.70 (m, 2H); 1.24 (s,3H); 0.95 (t, J = 7.0 Hz, 3H) 252. 2-(4-Fluoro-phenyl)-5- ¹H NMR inDMSO: (M + H)⁺ = 429 B <10 (2-hydroxy-propoxy)-6- 8.28 (d, J = 4.4 Hz,1H); 7.88 (dd, morpholin-4-yl- J-5.3 & 8.8 Hz, 2H); 7.32 (t,benzofuran-3- J = 8.8 Hz, 2H); 7.16 (s, 1H); carboxylic acid 7.06 (s,1H); 4.82 (d, J = 4.7 Hz, 1H); methylamide 4.00-3.90 (m, 3H); 3.74 (brs,4H); 3.04 (brs, 4H); 2.81 (d, J = 4.0 Hz, 3H); 1.19 (d, J = 4.7 Hz, 3H)253. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 479 A <1[(2-hydroxy-propyl)- 8.40 (d, J = 4.4 Hz, 1H); 7.94 (dd,methanesulfonyl- J = 8.8 & 5.3 Hz, 2H); 7.63 (brs, amino]-5-isopropoxy-1H); 7.36 (t, J = 8.8 Hz, 2H); benzofuran-3- 7.14 (s, 1H); 4.77 (septet,J = 6.1 Hz, carboxylic acid 1H); 4.62 (brs, 1H); methylamide 3.60-3.40(m, 3H); 3.00 (s, 3H); 2.81 (d, J = 4.4 Hz, 3H); 1.33 (d, J = 6.1 Hz254. 2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ = 482 A <1morpholin-4-yl-5-(1- 7.88 (dd, J = 8.8, 5.3 Hz, 2H);thiazol-2-yl-ethoxy)- 7.76 (d, J = 3.1 Hz, 1H); 7.33 (brs, 2H);benzofuran-3- 7.14 (t, J = 8.8 Hz, 2H); 7.08 (s, carboxylic acid 1H);5.82 (q, J = 6.6 Hz, 1H); methylamide 5.79 (brs, 1H); 3.83 (m, 4H); 3.15(m, 4H); 2.97 (d, J = 4.9 Hz, 3H); 1.78 (d, J = 6.1 Hz, 3H) 255.6-(Ethyl- ¹H NMR in CDCl₃: (M + H)⁺ = 449 A <1 methanesulfonyl- 7.83(dd, J = 8.3, 3.1 Hz, 2H); amino)-2-(4-fluoro- 7.51 (s, 1H); 7.40 (s,1H); 7.20 (t, phenyl)-5-isopropoxy- J = 8.3 Hz, 2H); 5.72 (brs, 1H);benzofuran-3- 4.78 (septet, J = 6.1 Hz, 1H); carboxylic acid 3.72 (brs,2H); 2.97 (d, J = 4.4 Hz, 3H); methylamide 2.96 (s, 3H); 1.40 (d, J =6.1 Hz, 6H); 1.13 (t, J = 7.0 Hz, 3H) 256. 6-(3,5-Dimethyl-1H- ¹H NMR inCDCl₃: (M + H)⁺ = 394.1 A <1 pyrazol-4-yl)-2-(4- 7.88 (m, 2H); 7.39 (s,1H); fluoro-phenyl)-5- 7.26 (s, 1H); 7.19 (m, 2H); 5.78 (brd,methoxy-benzofuran-3- 1H); 3.86 (s, 3H); 3.01 (d, carboxylic acid J =4.8 Hz, 3H); 2.25 (s, 6H) methylamide 257. 2-(4-Fluoro-phenyl)-5- ¹H NMRin CDCl₃: (M + H)⁺ = 408.1 A <1 isopropoxy-6-(5- 7.87 (m, 2H); 7.74 (s,1H); methyl-1H-pyrazol-4- 7.38 (s, 2H); 7.18 (m, 2H); 5.81 (brs,yl)-benzofuran-3- 1H); 4.52 (m, 1H); 3.00 (d, carboxylic acid J = 5.4Hz, 3H); 2.38 (s, 3H); methylamide 1.28 (d, J = 6.0 Hz, 6H) 258.3-[2-(4-Fluoro-phenyl)- ¹H NMR in DMSO: (M + H)⁺ = 434 A >303-methylcarbamoyl- 8.34 (brd, 1H, J = 4.10 Hz); benzofuran-5- 8.07 (s,1H); 7.92 (m, 3H); 7.76 (d, yloxymethyl]-benzoic 1H, J = 7.62 Hz); 7.56(m, 2H); acid methyl ester 7.35 (t, 2H, J = 7.03 Hz); 7.21 (d, 1H, J =2.34 Hz); 7.07 (dd, 1H, J = 8.79, 2.34 Hz); 5.24 (s, 2H); 3.86 (s, 3H);2.81 (d, 3H, J = 4.69 Hz) 259. 4-[2-(4-Fluoro-phenyl)- ¹H NMR in DMSO:(M − H)⁻ = 418 B <30 3-methylcarbamoyl- 8.38 (brd, 1H, J = 4.10 Hz);benzofuran-5- 7.90 (m, 4H); 7.56 (d, 1H, J = 8.79 Hz);yloxymethyl]-benzoic 7.35 (m, 4H); 7.20 (s, 1H); acid 7.05 (d, 1H, J =9.38 Hz); 5.13 (s, 2H); 2.82 (d, 3H, J = 4.69 Hz) 260.3-[2-(4-Fluoro-phenyl)- ¹H NMR in DMSO: (M − H)⁻ = 418 A >303-methylcarbamoyl- 12.98 (brs, 1H); 8.34 (br m, 1H); benzofuran-5- 8.05(s, 1H); 7.91 (m, 3H); yloxymethyl]-benzoic 7.72 (d, 1H, J = 6.45 Hz);7.56 (m, 2H); acid 7.35 (t, 2H, J = 8.79 Hz); 7.21 (s, 1H); 7.08 (d, 1H,J = 8.79 Hz); 5.23 (s, 2H); 2.81 (d, 3H, J = 6.71 Hz) 261.6-Acetyl-2-(4-fluoro- ¹H NMR in CDCl₃: (M + H)⁺ = 342.1 A <1phenyl)-5-methoxy- 7.84 (m, 2H); 7.83 (s, 1H); benzofuran-3- 7.37 (s,1H); 7.19 (m, 2H); 5.95 (brs, carboxylic acid 1H); 3.97 (s, 3H); 3.00(d, methylamide J = 4.8 Hz, 3H); 2.64 (s, 3H) 262.4-[2-(4-Fluoro-phenyl)- ¹H NMR in CDCl₃: (M + H)⁺ = 519 A <103-methylcarbamoyl-6- 8.09 (d, 2H, J = 8.21 Hz); morpholin-4-yl- 7.85 (m,2H); 7.57 (d, 2H, J = 8.21 Hz); benzofuran-5- 7.42 (s, 1H); 7.18 (t, 2H,yloxymethyl]-benzoic J = 8.21); 7.12 (s, 1H); 5.72 (brs, acid methylester 1H); 5.24 (s, 2H); 3.94 (s, 3H); 3.89 (m, 4H); 3.16 (m, 4H); 2.98(d, 3H, J = 4.69 Hz) 263. 3-[2-(4-Fluoro-phenyl)- ¹H NMR in CDCl₃: (M +H)⁺ = 519 A <10 3-methylcarbamoyl-6- 8.25 (s, 1H), 8.05 (d, 1H,morpholin-4-yl- J = 8.21 Hz); 7.87 (m, 2H); benzofuran-5- 7.67 (d, 1H, J= 7.62 Hz); 7.51 (t, 1H, yloxymethyl]-benzoic J = 7.62 Hz); 7.45 (s,1H); 7.20 (t, acid methyl ester 2H, J = 8.79 Hz); 7.13 (s, 1H); 5.75(brs, 1H); 5.24 (s, 2H); 3.97 (s, 3H); 3.93 (m, 4H); 3.18 (m, 4H); 3.00(d, 3H, J = 5.28) 264. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺= 436.1 B <10 isopropoxy-6-(1,3,5- 7.90 (m, 2H); 7.38 (s, 1H);trimethyl-1H-pyrazol-4- 7.25 (s, 1H); 7.18 (m, 2H); 5.78 (brs,yl)-benzofuran-3- 1H); 4.36 (m, 1H); 3.79 (s, 3H); carboxylic acid 3.01(d, J = 4.8 Hz, 3H); 2.17 (s, methylamide 3H); 2.14 (s, 3H); 1.20 (d, J= 6.0 Hz, 6H) 265. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ =397.1 C >30 isopropoxy-6- 7.82 (m, 2H); 7.52 (s, 1H); pyrrolidin-2-yl-7.32 (s, 1H); 7.18 (m, 2H); 6.76 (brs, benzofuran-3- 2H); 5.80 (brs,1H); 4.75 (m, carboxylic acid 1H); 4.72 (m, 1H); 3.28 (m, 2H);methylamide 2.97 (d, J = 5.4 Hz, 3H); 2.28 (m, 1H); 2.03 (m, 3H); 1.41(d, J = 6.0 Hz, 6H) 266. 6-Cyano-2-(4-fluoro- ¹H NMR in CDCl₃: (M + H)⁺= 325 A <1 phenyl)-5-methoxy- 7.89-7.83 (m, 2H); 7.83 (s, 1H);benzofuran-3- 7.45 (s, 1H); 7.25-7.20 (m, 2H); carboxylic acid 5.74 (s,1H); 3.99 (s, 3H); methylamide 2.99 (d, J = 5.6 Hz, 3H) 267.4-[2-(4-Fluoro-phenyl)- ¹H NMR in DMSO: (M + H)⁺ = 505 A <103-methylcarbamoyl-6- 8.32 (brd, 1H, J = 4.69 Hz); morpholin-4-yl- 7.90(m, 4H); 7.41-7.31 (m, 4H); benzofuran-5- 7.23 (s, 2H); 5.16 (s, 2H);yloxymethyl]-benzoic 3.75 (m, 4H); 3.07 (m, 4H); 2.84 (d, acid 3H, J =4.10) 268. 3-[2-(4-Fluoro-phenyl)- ¹H NMR in DMSO: (M + H)⁺ = 505 A <103-methylcarbamoyl-6- 8.33 (brd, 1H, J = 4.69 Hz); morpholin-4-yl- 8.02(s, 1H); 7.92 (m, 2H); 7.80 (d, benzofuran-5- 1H, J = 7.03 Hz);7.41-7.26 (m, yloxymethyl]-benzoic 4H); 7.23 (d, 2H, J = 4.10 Hz); acid5.16 (s, 2H); 3.76 (m, 4H); 3.07 (m, 4H); 2.84 (d, 3H, J = 4.10 Hz) 269.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 517 A <1 isopropoxy-6-8.43 (brd, 1H, J = 4.69); 7.92 (m, [methanesulfonyl-(1- 2H); 7.60 (s,1H); 7.37 (t, 2H, methyl-1H-tetrazol-5- J = 8.79 Hz); 7.14 (s, 1H); 5.19(s, ylmethyl)-amino]- 2H); 4.78 (m, 1H); 4.10 (s, 3H); benzofuran-3-3.20 (s, 3H); 2.82 (d, 3H, carboxylic acid J = 4.69 Hz); 1.35 (d, 6H,methylamide J = 6.45 Hz) 270. 4-({[2-(4-Fluoro- ¹H NMR in CDCl₃: (M +H)⁺ = 569 A <1 phenyl)-5-isopropoxy- 7.91 (d, 2H, J = 8.21 Hz); 7.75 (m,3-methylcarbamoyl- 2H); 7.41 (s, 1H); 7.34 (d, 2H, benzofuran-6-yl]- J =8.21 Hz); 7.20-7.14 (m, 3H); methanesulfonyl- 5.66 (brs, 1H); 4.84 (brm, 3H); amino}-methyl)-benzoic 3.87 (s, 3H); 3.04 (s, 3H); acid methylester 2.94 (d, 3H, J = 5.27 Hz); 1.48 (d, 6H, J = 5.86 Hz) 271.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 532 A <10isopropoxy-6- 7.80 (m, 2H); 7.43 (s, 1H); [methanesulfonyl-(2- 7.39 (s,1H); 7.18 (t, 2H, J = 8.79 Hz); methyl-thiazol-4- 7.07 (s, 1H); 5.68(brs, 1H); ylmethyl)-amino]- 4.93 (brs, 2H); 4.78 (m, 1H); 3.06 (s,benzofuran-3- 3H); 2.95 (d, 3H, J = 4.69 Hz); carboxylic acid 2.63 (s,3H); 1.43 (d, 6H, methylamide J = 6.45 Hz) 272. 4-({[2-(4-Fluoro- ¹H NMRin DMSO: (M + H)⁺ = 555 A ≦1.0 phenyl)-5-isopropoxy- 8.36 (brd, 1H, J =4.69 Hz); 3-methylcarbamoyl- 7.89-7.82 (m, 4H); 7.40 (m, 3H);benzofuran-6-yl]- 7.32 (t, 2H, J = 8.79 Hz); 7.10 (s, 1H);methanesulfonyl- 4.80 (br m, 3H); 3.13 (s, 3H); amino}-methyl)-benzoic2.79 (d, 3H, J = 4.10 Hz); 1.38 (d, acid 6H, J = 5.86 Hz) 273.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 439.05 A <1isopropoxy-6-(5- 8.43 (q, J = 4.4 Hz, 1H); 7.98 (s, methoxymethyl- 1H);7.97 (dd, J = 5.3, 8.8 Hz, isoxazol-3-yl)- 2H); 7.39 (apparent triplet,J = 8.8 Hz, benzofuran-3- 2H); 7.29 (s, 1H); 6.93 (s, carboxylic acid1H); 4.76 (m, J = 6.1, 5.7 Hz, methylamide 1H); 4.62 (s, 2H); 3.36 (s,3H); 2.85 (d, J = 4.4 Hz, 3H); 1.34 (d, J = 6.1 Hz, 6H) 274.6-(5-Cyclopropyl- ¹H NMR in DMSO: (M + H)⁺ = 435.12 A <1isoxazol-3-yl)-2-(4- 8.42 (q, J = 4.4 Hz, 1H); 7.96 (dd,fluoro-phenyl)-5- J = 5.3, 8.8 Hz, 2H); 7.92 (s, 1H);isopropoxy-benzofuran- 7.38 (apparent triplet, J = 8.8 Hz, 3-carboxylicacid 2H); 7.26 (s, 1H); 6.61 (s, 1H); methylamide 4.72 (m, J = 6.15 Hz,1H); 2.84 (d, J = 4.4 Hz, 3H); 2.22 (m, 1H); 1.33 (d, J = 6.15 Hz, 6H);1.10 (m, 2H); 0.94 (m, 2H) 275. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃:(M + H)⁺ = 475.1 A <1 isopropoxy-6-(1- 7.84 (m, 2H); 7.56 (s, 1H);methanesulfonyl- 7.30 (s, 1H); 7.21 (m, 2H); 5.73 (brs,pyrrolidin-2-yl)- 1H); 5.21 (dd, J = 8.4 Hz, 2.4 Hz, benzofuran-3- 1H);4.69 (m, 1H); 3.70 (m, 1H); carboxylic acid 3.55 (m, 1H); 2.97 (d, J =3.9 Hz, methylamide 3H); 2.84 (s, 3H); 2.35 (m, 1H); 1.95 (m, 3H); 1.39(d, J = 6.3 Hz) 276. 6-Acetyl-2-(4-fluoro- ¹H NMR in CDCl₃: (M + H)⁺ =328.0 B <10 phenyl)-5-hydroxy- 12.16 (s, 1H); 8.03 (m, 2H);benzofuran-3- 7.87 (s, 1H); 7.19 (m, 2H); 5.86 (br, carboxylic acid 1H);3.02 (d, J = 4.8 Hz, 3H); methylamide 2.71 (s, 3H) 277. 6-(Ethyl- ¹H NMRin DMSO: (M + H)⁺ = 421.1 A <1 methanesulfonyl- 8.43 (d, J = 4.69 Hz,1H); amino)-2-(4-fluoro- 7.96-7.91 (m, 2H); 7.6 (s, 1H); 7.38 (t,phenyl)-5-methoxy- J = 8.79 Hz, 2H); 7.21 (s, 1H); benzofuran-3- 3.9 (s,3H); 3.62 (q, J = 7.03, 2H); carboxylic acid 3.02 (s, 3H); 2.84 (d, J =4.69 Hz, methylamide 3H); 1.02 (t, J = 7.03 Hz, 3H) 278.4-[2-(4-Fluoro-phenyl)- ¹H NMR in DMSO: (M + H)⁺ = 440 A <105-methoxy-3- 8.36 (q, 1H, br); 8.00 (q, 1H, br); methylcarbamoyl-7.97-7.68 (m, 3H); 7.53 (s, 1H); benzofuran-6-yl]-2-oxo- 7.77 (m, 2H);7.11 (s, 1H); pyrrolidine-3-carboxylic 4.20 (q, 1H); 3.84 (s, 3H); 3.57(m, acid methylamide 2H); 3.16 (t, 1H); 2.82 (d, 3H); 2.57 (d, 3H) 279.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 395.0 A <30isopropoxy-6-(4H- 8.47 (s, 1H); 8.03 (s, 1H); [1,2,4]triazol-3-yl)-7.84-7.89 (m, 2H); 7.57 (s, 1H); benzofuran-3- 7.19-7.25 (t, 2H, J =8.79 Hz); carboxylic acid 5.80 (br.s, 1H); 4.90-4.98 (septet, 1H,methylamide J = 5.86 Hz); 2.98-3.00 (d, 3H, J = 4.69 Hz); 1.52-1.54 (d,6H, J = 6.45 Hz) 280. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ =425 A <1 methoxy-6-(5- 7.86 (dd, J = 8.8 and 5.1 Hz, 2H);methoxymethyl-3- 7.43 (s, 1H); 7.35 (s, 1H); methyl-isoxazol-4-yl)- 7.21(apparent t, J = 8.8 and 8.4 Hz, benzofuran-3- 2H); 5.78 (brs 1H); 4.42(s, 2H); carboxylic acid 3.86 (s, 3H); 3.36 (s, 3H); methylamide 3.01(d, J = 5.1 Hz, 3H); 2.21 (s, 3H) 281. 2-(4-Fluoro-phenyl)-5- ¹H NMR inCDCl₃: (M − H)⁻ = 539 A <1 isopropoxy-6- 7.76 (m, 2H); 7.38 (s, 1H);[methanesulfonyl-(4- 7.20-7.12 (m, 5H); 6.75 (d, 2H, methoxy-benzyl)- J= 8.79 Hz); 5.86 (brs, 1H); amino]-benzofuran-3- 4.90-4.70 (br m, 3H);3.74 (s, 3H); carboxylic acid 3.03 (s, 3H); 2.95 (d, 3H, J = 4.69 Hz);methylamide 1.47 (d, 6H, J = 6.45 Hz) 282. 2-(4-Fluoro-phenyl)-5- ¹H NMRin CDCl₃: (M − H)⁻ = 514 A <1 isopropoxy-6- 7.79 (m, 2H); 7.42 (s, 1H);[methanesulfonyl-(5- 7.34 (s, 1H); 7.19 (t, 2H, J = 8.79 Hz);methyl-isoxazol-3- 6.21 (s, 1H); 5.86 (brs, 1H); ylmethyl)-amino]- 4.83(br m, 3H); 3.04 (s, 3H); 2.96 (d, benzofuran-3- 3H, J = 4.69 Hz); 2.38(s, 3H); carboxylic acid 1.45 (d, 6H, J = 5.86 Hz) methylamide 283.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: *** A <1 isopropoxy-6-(5- 8.015(s, 1H); 7.87 (dd, J = 5.3, methyl-isoxazol-3-yl)- 8.3 Hz, 2H); 7.43 (s,1H); benzofuran-3- 7.19 (apparent triplet, d, J = 8.3 Hz, carboxylicacid 2H); 6.58 (s, 1H); 5.79 (brs, 1H); methylamide 4.68 (m, 1H); 2.99(d, J = 4.8 Hz, 3H); 2.48 (s, 3H); 1.38 (d, J = 5.7 Hz, 6H) 284.6-[(3,5-Dimethyl- ¹H NMR in DMSO: (M + H)⁺ = 530 A <10isoxazol-4-ylmethyl)- 8.41 (brd, 1H, J = 4.69 Hz); methanesulfonyl- 7.91(m, 2H); 7.36 (m, 3H); 7.12 (s, amino]-2-(4-fluoro- 1H); 4.79 (m, 1H);4.64 (br m, phenyl)-5-isopropoxy- 2H); 3.13 (s, 3H); 2.82 (d, 3H,benzofuran-3- J = 4.69 Hz); 2.08 (s, 3H); 2.05 (s, carboxylic acid 3H);1.37 (d, 6H, J = 5.86 Hz) methylamide 285. 2-(4-Fluoro-phenyl)-5- ¹H NMRin DMSO: (M + H)⁺ = 518 A <1 isopropoxy-6- 8.42 (brd, 1H, J = 4.69 Hz);(methanesulfonyl- 7.92 (m, 2H); 7.67 (d, 1H, J = 3.52 Hz);thiazol-2-ylmethyl- 7.65 (d, 1H, J = 3.52 Hz); amino)-benzofuran-3- 7.45(s, 1H); 7.36 (t, 2H, J = 8.79 Hz); carboxylic acid 7.18 (s, 1H); 5.12(brs, 2H); methylamide 4.83 (m, 1H); 3.16 (s, 3H); 2.82 (d, 3H, J = 4.69Hz); 1.39 (d, 6H, J = 6.45 Hz) 286. 2-({[2-(4-Fluoro- ¹H NMR in DMSO:(M + H)⁺ = 590 A <10 phenyl)-5-isopropoxy- 8.49 (s, 1H); 8.42 (brd, 1H,3-methylcarbamoyl- J = 4.10 Hz); 7.93 (m, 2H); benzofuran-6-yl]- 7.54(s, 1H); 7.37 (t, 2H, J = 8.79 Hz); methanesulfonyl- 7.20 (s, 1H); 5.13(brs, 2H); amino}-methyl)- 4.84 (m, 1H); 4.25 (q, 2H, J = 7.03 Hz);thiazole-4-carboxylic 3.18 (s, 3H); 2.82 (d, 3H, acid ethyl ester J =4.69 Hz); 1.39 (d, 6H, J = 6.45 Hz); 1.26 (t, 3H, J = 7.03 Hz) 287.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 393 A <10 hydroxy-6-9.98 (s, 1H); 8.39 (d, J = 4.4 Hz, (methanesulfonyl- 1H); 7.91 (m, 2H);7.51 (s, 1H); methyl-amino)- 7.35 (t, J = 8.8 Hz, 2H); 7.09 (s,benzofuran-3- 1H); 3.20 (s, 3H); 3.08 (s, 3H); carboxylic acid 2.80 (d,J = 4.4 Hz, 3H) methylamide 288. 6-(Allyl- ¹H NMR in DMSO: (M + H)⁺ =459 A <1 methanesulfonyl- 8.40 (d, J = 4.7 Hz, 1H); 7.93 (dd,amino)-5-allyloxy-2-(4- J = 9.0, 5.3 Hz, 2H); 7.57 (s, 1H);fluoro-phenyl)- 7.35 (t, J = 9.0 Hz, 2H); 7.33 (s, benzofuran-3- 1H);6.10 (m, 1H); 5.80 (m, 1H); carboxylic acid 5.50 (m, 1H); 5.30 (m, 1H);methylamide 5.10 (m, 1H); 5.00 (m, 1H); 4.70 (d, J = 3.5 Hz, 2H); 4.20(brs, 2H); 3.05 (s, 3H); 2.81 (d, J = 4.7 Hz, 3H) 289. 6-(Acetyl- ¹H NMRin DMSO: (M + H)⁺ = 435.0 A <1 methanesulfonyl- 8.48 (d, J = 4.39 Hz,1H); amino)-2-(4-fluoro- 7.96-7.91 (m, 2H); 7.86 (s, 1H);phenyl)-5-methoxy- 7.39 (t, J = 8.79 Hz, 2H); 7.27 (s, 1H);benzofuran-3- 3.93 (s, 3H); 3.49 (s, 3H); carboxylic acid 2.84 (d, J =4.39, 3H); 1.89 (s, 3H) methylamide 290. 6-[(3,5-Dimethyl- ¹H NMR inDMSO: (M + H)⁺ = 502.1 A <10 isoxazol-4-ylmethyl)- 8.44 (m, 1H);7.94-7.90 (m, methanesulfonyl-amino]- 2H); 7.43-7.33 (m, 3H); 7.16 (s,2-(4-fluoro-phenyl)-5- 1H); 4.67 (brs, 2H); 3.9 (s, 3H);methoxy-benzofuran-3- 3.13 (m, 3H); 2.84-2.82 (m, carboxylic acid 3H);2.11 (d, J = 3.52 Hz, 3H); methylamide 2.06 (d, J = 3.52, 3H) 291.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 490.0 A <1(methanesulfonyl- 9.01 (s, 1H); 8.41 (d, J = 4.84 Hz,thiazol-4-ylmethyl- 1H); 7.93-7.88 (m, 2H); amino)-5-methoxy- 7.55 (m,1H); 7.48 (s, 1H); 7.36 (t, benzofuran-3-carboxylic J = 8.35 Hz, 2H);7.17 (s, 1H); acid methylamide 4.93 (brs, 2H); 3.90 (s, 3H); 3.15 (s,3H); 2.83 (d, J = 4.84 Hz, 3H) 292. 2-({[2-(4-Fluoro- ¹H NMR in DMSO:(M + H)⁺ = 562 A >100 phenyl)-5-isopropoxy-3- 8.42 (brm, 2H); 7.93 (m,2H); methylcarbamoyl- 7.53 (d, 1H, J = 1.17 Hz); 7.36 (t,benzofuran-6-yl]- 2H, J = 8.79 Hz); 7.19 (s, 1H);methanesulfonyl-amino}- 5.12 (brs, 2H); 4.84 (m, 1H);methyl)-thiazole-4- 3.19 (s, 3H); 2.82 (d, 3H, J = 3.52 Hz); carboxylicacid 1.39 (d, 6H, J = 5.28 Hz) 293. 5-(2,2-Dimethyl-4-oxo- ¹H NMR inDMSO: (M + H)⁺ = 561 B <10 4H-benzo[1,3]dioxin-5- 8.32 (brd, 1H, J =4.40 Hz); ylmethoxy)-2-(4-fluoro- 8.08 (s, 1H); 7.90 (m, 2H); 7.80 (d,phenyl)-6-morpholin-4- 1H, J = 8.79 Hz); 7.35 (t, 2H, yl-benzofuran-3- J= 8.79 Hz); 7.26-7.19 (m, 3H); carboxylic acid 5.20 (s, 2H); 3.77 (m,4H); methylamide 3.06 (m, 4H); 2.83 (d, 3H, J = 4.00 Hz); 1.72 (s, 6H)294. 5-(2,2-Dimethyl-4-oxo- ¹H NMR in DMSO: (M + H)⁺ = 597 A <14H-benzo[1,3]dioxin-5- 8.42 (brd, 1H, J = 4.40 Hz); ylmethoxy)-6-(ethyl-8.05 (d, 1H, J = 1.76 Hz); 7.93 (m, methanesulfonyl-amino)- 2H); 7.85(d, 1H, J = 8.35 Hz); 2-(4-fluoro-phenyl)- 7.65 (s, 1H); 7.39 (t, 2H, J= 8.79 Hz); benzofuran-3-carboxylic 7.34 (s, 1H); 7.19 (d, 1H, acidmethylamide J = 8.35 Hz); 5.26 (s, 2H); 3.63 (m, 2H); 2.93 (s, 3H); 2.84(d, 3H, J = 4.40 Hz); 1.71 (s, 6H); 1.03 (t, 3H, J = 7.03 Hz) 295.2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ = 466 A <10(1H-imidazol-4-yl)-5- 7.96-7.85 (m, 3H); 7.74 (s, 1H);methoxy-benzofuran-3- 7.61 (s, 1H); 7.45 (s, 1H); carboxylic acid7.24-7.18 (m, 2H); 5.82 (s, 1H); methylamide 4.04 (s, 3H); 3.0 (d, J =4.8 Hz, 3H) 296. 2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ = 466A <1 (1H-imidazol-2-yl)-5- 10.6 (s, 1H); 8.48 (s, 1H);methoxy-benzofuran-3- 7.88-7.84 (m, 2H); 7.50 (s, 1H); carboxylic acid7.26-7.20 (m, 3H); 7.18 (s, 1H); methylamide 7.13 (s, 1H); 5.84 (s, 1H);4.14 (s, 3H); 3.0 (d, J = 6.8 Hz, 3H) 297. 6-(Ethyl- ¹H NMR in DMSO: (M− H)⁻ = 405 A <10 methanesulfonyl-amino)- 9.96 (s, 1H); 8.40 (d, J = 4.4Hz, 2-(4-fluoro-phenyl)-5- 1H); 7.92 (dd, J = 8.8, 5.3 Hz,hydroxy-benzofuran-3- 2H); 7.46 (s, 1H); 7.37 (t, carboxylic acid J =8.8 Hz, 2H); 7.09 (s, 1H); methylamide 3.60 (q, J = 7.0 Hz, 2H); 3.01(s, 3H); 2.80 (d, J = 4.4 Hz, 3H); 1.00 (t, J = 7.0 Hz, 3H) 298.5-Difluoromethoxy-2-(4- ¹H NMR in CDCl₃: (M + H)⁺ = 443 A <1fluoro-phenyl)-6- 7.86 (dd, J = 8.8, 5.3 Hz, 2H); (methanesulfonyl- 7.70(s, 1H); 7.62 (s, 1H); methyl-amino)- 7.24 (t, J = 8.8 Hz, 2H); 6.69 (t,benzofuran-3-carboxylic J = 73.4 Hz, 1H); 5.74 (brs, 1H); acidmethylamide 3.33 (s, 3H); 3.03 (s, 3H); 2.98 (d, J = 4.8 Hz, 3H) 299.2-(4-Fluoro-phenyl)-6- *** (M + H)⁺ = 484 A <1 (methanesulfonyl-pyridin-4-ylmethyl- amino)-5-methoxy- benzofuran-3-carboxylic acidmethylamide 300. 2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ =342.1 A <10 (1-hydroxy-1-methyl- 7.95 (m, 2H); 7.69 (s, 1H);ethyl)-5-methyl- 7.56 (s, 1H); 7.16 (m, 2H); 5.83 (brs,benzofuran-3-carboxylic 1H); 3.02 (d, J = 4.6 Hz, 3H); acid methylamide2.69 (s, 1H); 2.64 (d, J = 3.9 Hz, 3H); 1.72 (s, 6H) 301.6-Acetyl-2-(4-fluoro- ¹H NMR in CDCl₃: (M + H)⁺ = 326.1 A <10phenyl)-5-methyl- 7.94 (m, 2H); 7.79 (s, 1H); benzofuran-3-carboxylic7.69 (s, 1H); 7.20 (m, 2H); 5.83 (brs, acid methylamide 1H); 3.02 (d, J= 4.8 Hz, 3H); 2.64 (s, 3H); 2.96 (s, 3H) 302. 5-(2,2-Dimethyl-4-oxo- ¹HNMR in DMSO: (M + H)⁺ = 583 A <1 4H-benzo[1,3]dioxin-7- 8.39 (brd, 1H, J= 4.69 Hz); ylmethoxy)-2-(4-fluoro- 7.92 (m, 3H); 7.74 (s, 1H); 7.37 (m,phenyl)-6- 3H); 7.29 (d, 2H, J = 1.76 Hz); (methanesulfonyl- 5.32 (brs,2H); 3.23 (s, 3H); methyl-amino)- 3.01 (s, 3H); 2.82 (d, 3H, J = 4.10Hz); benzofuran-3-carboxylic 1.71 (s, 6H) acid methylamide 303.2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ = 435 A <1[1-(methanesulfonyl- 7.89-7.84 (m, 2H); 7.50 (s, 1H);methyl-amino)-ethyl]-5- 7.39 (s, 1H); 7.27-7.19 (m, 2H);methoxy-benzofuran-3- 5.76 (s, 1H); 5.63-5.56 (m, 1H); carboxylic acid3.95 (s, 3H); 3.00 (d, J = 4.8 Hz, methylamide 3H); 2.82 (s, 3H); 2.69(s, 3H); 1.65 (d, J = 6.9 Hz, 3H) 304. 2-(4-Fluoro-phenyl)-5- ¹H NMR inCDCl₃: (M + H)⁺ = 357 B >30 methoxy-6-(1- 7.88-7.83 (m, 3H); 7.47 (s,1H); methylamino-ethyl)- 7.33 (s, 1H); 7.21-7.16 (m, 6H);benzofuran-3-carboxylic 5.75 (s, 1H); 4.20-4.16 (m, 1H); acidmethylamide 3.92 (s, 3H); 3.47 (s, 1H); 2.99 (d, J = 4.5 Hz, 3H); 2.34(s, 3H); 1.44 (d, J = 6.3 Hz, 3H) 305. 4-[2-(4-Fluoro-phenyl)- ¹H NMR inDMSO: (M + H)⁺ = 541 A <1 6-(methanesulfonyl- 8.40 (brd, 1H, J = 4.69);8.02 (d, methyl-amino)-3- 2H, J = 8.21); 7.93 (m, 2H); methylcarbamoyl-7.70 (m, 3H); 7.39 (t, 2H, J = 8.79 Hz); benzofuran-5- 7.34 (s, 1H);5.34 (s, 2H); yloxymethyl]-benzoic 3.87 (s, 3H); 3.22 (s, 3H); acidmethyl ester 2.97 (s, 3H); 2.84 (d, 3H, J = 4.10 Hz) 306.2-[2-(4-Fluoro-phenyl)- ¹H NMR in DMSO: (M + H)⁺ = 541 A <16-(methanesulfonyl- 8.39 (brd, 1H, J = 5.28 Hz); methyl-amino)-3- 8.15(s, 1H); 7.93 (m, 3H); 7.82 (d, methylcarbamoyl- 1H, J = 7.62 Hz); 7.68(s, 1H); benzofuran-5- 7.58 (t, 1H, J = 7.62 Hz); 7.37 (m,yloxymethyl]-benzoic 3H); 5.32 (s, 2H); 3.86 (s, 3H); acid methyl ester3.20 (s, 3H); 2.94 (s, 3H); 2.82 (d, 3H, J = 4.10 Hz) 307.6-[(2-Fluoro-ethyl)- ¹H NMR in DMSO: (M + H)⁺ = 439 A <1methanesulfonyl-amino]- 8.43 (m, 1H); 7.93 (dd, J = 5.3 &2-(4-fluoro-phenyl)-5- 8.8 Hz, 2H); 7.62 (s, 1H); 7.39 (t,methoxy-benzofuran-3- J = 8.8 Hz, 2H); 7.22 (s, 1H); carboxylic acid4.54 (t, J = 5.3 Hz, 1H); 4.39 (t, methylamide J = 4.7 Hz, 1H); 3.92 (m,4H); 3.84 (m, 1H); 3.06 (s, 3H); 2.83 (d, J = 4.7 Hz, 3H) 308.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 475 A <1[methanesulfonyl-(2,2,2- 8.45 (m, 1H); 7.93 (dd, J = 5.3 &trifluoro-ethyl)-amino]-5- 8.8 Hz, 2H); 7.65 (s, 1H); 7.39 (t,methoxy-benzofuran-3- J = 8.8 Hz, 2H); 7.25 (s, 1H); carboxylic acid4.40 (m, 2H); 3.94 (s, 3H); 3.10 (s, methylamide 3H); 2.83 (d, J = 4.7Hz, 3H) 309. 2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: M⁺ = 446 (GC/MS) A<1 (1-methanesulfonyl- 7.84 (m, 2H); 7.58 (s, 1H); pyrrolidin-2-yl)-5-7.26 (s, 1H); 7.18 (m, 2H); 5.76 (brs, methoxy-benzofuran-3- 1H); 5.22(m, 1H); 3.91 (s, 3H); carboxylic acid 3.75 (m, 1H); 3.55 (m, 1H);methylamide 3.18 (m, 1H); 3.00 (d, J = 4.6 Hz, 3H); 2.84 (s, 3H); 1.92(m, 2H); 1.84 (m, 2H) 310. 6-(3-Cyclopropyl-5- ¹H NMR in CDCl₃: (M − H)⁻= 449 A <1 methoxymethyl-isoxazol- 7.87 (dd, J = 8.8 and J = 5.1 Hz,4-yl)-2-(4-fluoro- 2H); 7.44 (s, 1H); 7.42 (s, 1H); phenyl)-5-methoxy-7.20 (apparent t, J = 8.8 and 8.4 Hz, benzofuran-3-carboxylic 2H); 5.81(brs, 1H); 4.40 (s, acid methylamide 2H); 3.87 (s, 3H); 3.34 (s, 3H);3.01 (d, J = 4.8 Hz, 3H); 1.65 (m, 1H); 1.02 (m, 2H); 0.88 (m, 2H) 311.4-[2-(4-Fluoro-phenyl)- ¹H NMR in DMSO: (M + H)⁺ = 527 A <106-(methanesulfonyl- 8.41 (brd, 1H, J = 4.10 Hz); methyl-amino)-3- 7.95(m, 4H); 7.69 (s, 1H); 7.58 (d, methylcarbamoyl- 2H, J = 8.21 Hz); 7.37(m, 3H); benzofuran-5- 5.29 (s, 2H); 3.21 (s, 3H); yloxymethyl]-benzoic2.94 (s, 3H); 2.84 (d, 3H, J = 4.69 Hz) acid 312.3-[2-(4-Fluoro-phenyl)- ¹H NMR in DMSO: (M + H)⁺ = 527 A <16-(methanesulfonyl- 8.41 (brd, 1H, J = 4.10 Hz); methyl-amino)-3- 8.14(s, 1H); 7.94 (m, 3H); 7.80 (d, methylcarbamoyl- 1H, J = 7.62 Hz); 7.69(s, 1H); benzofuran-5- 7.57 (t, 1H, J = 8.21 Hz); 7.38 (m,yloxymethyl]-benzoic 3H); 5.33 (s, 2H); 3.22 (s, 3H); acid 2.95 (s, 3H);2.84 (d, 3H, J = 4.10 Hz) 313. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃:(M + H)⁺ = 411 A <1 methoxy-6-(5- 8.03 (s, 1H); 7.87 (dd, J = 5.27 &methoxymethyl-isoxazol- 8.8 Hz, 2H); 7.45 (s, 1H); 3-yl)-benzofuran-3-7.20 (apparent triplet, J = 8.8 & 8.3 Hz, carboxylic acid 2H); 6.83 (s,1H); 5.80 (brs, methylamide 1H); 4.61 (s, 2H); 3.96 (s, 3H); 3.48 (s,3H); 3.00 (d, J = 4.8 Hz, 3H) 314. 6-(3,5-Dimethyl- ¹H NMR in CDCl₃:(M + H)⁺ = 381 A <1 isoxazol-4-yl)-2-(4- 7.90 (m, 2H); 7.56 (s, 1H);fluoro-phenyl)-5- 7.22 (m, 3H); 6.04 (brs, 1H); hydroxy-benzofuran-3-5.83 (brs, 1H); 3.00 (d, 3H, carboxylic acid J = 4.69 Hz); 2.36 (s, 3H);2.22 (s, methylamide 3H) 315. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO:(M + H)⁺ = 383 A <10 methoxy-6-(5-oxo- 8.36 (m, 1H, br); 7.92 (dd, 2H);pyrrolidin-3-yl)- 7.64 (s, 1H, br); 7.54 (s, 1H);benzofuran-3-carboxylic 7.34 (dd, 2H); 7.11 (s, 1H); acid methylamide3.89 (m, 1H); 3.86 (s, 3H); 3.6 (m, 1H); 3.21 (m, 2H); 2.81 (d, 3H);2.48-2.37 (m, 2H) 316. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ =505 B <1 [methanesulfonyl-(2- 8.42 (m, 1H); 7.94 (dd, J = 5.9 &trifluoromethoxy-ethyl)- 8.8 Hz, 2H); 7.57 (s, 1H); 7.38 (t,amino]-5-methoxy- J = 8.8 Hz, 2H); 7.23 (s, 1H); benzofuran-3-carboxylic4.11 (m, 2H); 3.92 (m, 5H); 3.06 (s, acid methylamide 3H); 2.84 (d, J =4.7 Hz, 3H) 317. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 365C <1 methoxy-6-(1H-pyrrol-3- 8.32 (m, 1H); 7.89 (m, 2H);yl)-benzofuran-3- 7.66 (s, 1H); 7.42 (m, 1H); 7.33 (s, carboxylic acid1H); 7.25 (m, 2H); 6.86 (m, methylamide 1H); 6.67 (m, 1H); 5.81 (q, 1H);3.96 (s, 3H); 3.01 (d, 3H) 318. 6-(3,5-Dimethyl- ¹H NMR in CDCl₃: (M +H)⁺ = 439.1 A >30 isoxazol-4-yl)-2-(2- 7.63 (s, 1H); 7.54-7.60 (m, 1H);ethoxy-4-fluoro-phenyl)- 7.24-7.26 (m, 1H); 7.227 (s,5-methoxy-benzofuran-3- 1H); 6.80-6.86 (t of d, 1H, carboxylic acid J =2.34 Hz & 8.21 Hz); methylamide 6.75-6.79 (d of d, 1H,); J = 2.34 &11.14 Hz); 5.80 (brs 1H); 4.05-4.12 (q, 2H, J = 7.03 Hz); 3.87 (s, 3H);2.32 (s, 3H); 2.18 (s, 3H); 1.37-1.42 (t, 3H, J = 7.03 Hz) 319.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 490 B <1(methanesulfonyl- 9.17 (d, 1H, J = 1.76 Hz); methyl-amino)-5- 8.40 (brd,1H, J = 4.69 Hz); 7.95 (m, (thiazol-4-ylmethoxy)- 2H); 7.86 (d, 1H, J =2.34 Hz); benzofuran-3-carboxylic 7.65 (s, 1H); 7.39 (m, 3H); acidmethylamide 5.39 (s, 2H); 3.20 (s, 3H); 2.97 (s, 3H); 2.85 (d, 3H, J =4.69 Hz) 320. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 504 A <1(methanesulfonyl- 8.41 (brd, 1H, J = 4.10 Hz); methyl-amino)-5-(2- 7.95(m, 2H); 7.64 (s, 1H); 7.60 (s, methyl-thiazol-4- 1H); 7.38 (m, 3H);5.28 (s, 2H); ylmethoxy)-benzofuran- 3.20 (s, 3H); 3.00 (s, 3H);3-carboxylic acid 2.85 (d, 3H, J = 4.69 Hz); 2.68 (s, 3H) methylamide321. 5-(3-Chloromethyl- ¹H NMR in DMSO: (M + H)⁺ = 524.9 A <1[1,2,4]thiadiazol-5- 8.49 (brd, 1H, J = 4.69 Hz); yloxy)-2-(4-fluoro-8.19 (s, 1H); 7.99 (m, 2H); 7.90 (s, phenyl)-6- 1H); 7.43 (t, 2H, J =8.79 Hz); (methanesulfonyl- 4.74 (s, 2H); 3.16 (s, 3H); methyl-amino)-3.10 (s, 3H); 2.82 (d, 3H, J = 4.10 Hz) benzofuran-3-carboxylic acidmethylamide 322. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 559 A<1 {[2-(4-fluoro-phenyl)-2- 8.40 (d, J = 4.4 Hz, 1H); 7.90 (m,hydroxy-ethyl]- 2H); 7.37 (t, J = 8.8 Hz, 2H); methanesulfonyl-amino}-7.30-7.10 (m, 6H); 5.50 (m, 5-isopropoxy- 1H); 4.78 (septet, J = 6.1 Hz,1H); benzofuran-3-carboxylic 4.50 (m, 1H); 3.90 (m, 1H); acidmethylamide 3.42 (m, 1H); 3.00 (s, 3H); 2.82 (d, J = 4.2 Hz, 3H); 1.31(d, J = 6.1 Hz, 6H) 323. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺= 381 A <1 methoxy-6-(2-methyl- 8.46-8.48 (d, 1H, J = 4.69 Hz);2H-[1,2,4]triazol-3-yl)- 8.01 (s, 1H); 7.94-7.99 (m, 2H);benzofuran-3-carboxylic 7.71 (s, 1H); 7.36-7.43 (t, 2H, acid methylamideJ = 8.79 Hz); 7.31 (s, 1H); 3.89 (s, 3H); 3.69 (s, 3H); 2.86-2.87 (d,3H, J = 4.69 Hz) 324. 5-(3,5-Dimethyl- ¹H NMR in DMSO: (M + H)⁺ = 502 A<1 isoxazol-4-ylmethoxy)-2- 8.45 (brd, 1H, J = 4.69 Hz);(4-fluoro-phenyl)-6- 7.94 (m, 2H); 7.70 (s, 1H); 7.39 (m,(methanesulfonyl- 3H); 5.05 (s, 2H); 3.14 (s, 3H); methyl-amino)- 2.94(s, 3H); 2.85 (d, 3H, benzofuran-3-carboxylic J = 4.10 Hz); 2.44 (s,3H); 2.27 (s, acid methylamide 3H) 325. 2-(4-Fluoro-phenyl)-6- ¹H NMR inDMSO: (M + H)⁺ = 513 A <1 (methanesulfonyl- 8.40 (brd, 1H, J = 4.10 Hz);methyl-amino)-5-(3- 7.93 (m, 2H); 7.70 (s, 1H); methoxy-benzyloxy)-7.42-7.31 (m, 4H); 7.12 (m, 2H); benzofuran-3-carboxylic 6.92 (d, 1H, J= 8.21 Hz); 5.21 (s, 2H); acid methylamide 3.77 (s, 3H); 3.21 (s, 3H);2.97 (s, 3H); 2.84 (d, 3H, J = 4.10 Hz) 326. 2-(4-Fluoro-phenyl)-5- ¹HNMR in DMSO: (M + H)⁺ = 435 B <30 hydroxy-6-(isobutyl- 10.05 (s, 1H);8.40 (d, J = 4.4 Hz, methanesulfonyl-amino)- 1H); 7.93 (dd, J = 5.3 &8.8 Hz, benzofuran-3-carboxylic 2H); 7.48 (s, 1H); 7.35 (t, acidmethylamide J = 8.8 Hz, 2H); 7.10 (s, 1H); 3.40 (d, J = 7.5 Hz, 2H);2.98 (s, 3H); 2.80 (d, J = 4.4 Hz, 3H); 1.50 (m, 1H); 0.88 (d, J = 6.6Hz, 6H) 327. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 513 A <1(methanesulfonyl- 8.40 (brd, 1H, J = 4.69 Hz); methyl-amino)-5-(4- 7.94(m, 2H); 7.66 (s, 1H); 7.47 (d, methoxy-benzyloxy)- 2H, J = 8.79 Hz);7.39 (m, 3H); benzofuran-3-carboxylic 6.98 (d, 2H, J = 8.79 Hz); 5.15(s, acid methylamide 2H); 3.78 (s, 3H); 3.17 (s, 3H); 2.90 (S, 3H); 2.85(d, 3H, J = 4.69 Hz) 328. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M +H)⁺ = 484 A <1 (methanesulfonyl- 8.62 (d, 2H, J = 5.86 Hz);methyl-amino)-5- 8.40 (brd, 1H, J = 4.69 Hz); 7.93 (m,(pyridin-4-ylmethoxy)- 2H); 7.74 (s, 1H); 7.55 (d, 2H,benzofuran-3-carboxylic J = 5.28 Hz); 7.39 (t, 2H, acid methylamide J =8.79 Hz); 7.31 (s, 1H); 5.32 (s, 2H); 3.26 (s, 3H); 3.02 (s, 3H); 2.83(d, 3H, J = 4.69 Hz) 329. 5-(2,2-Dimethyl-4-oxo- ¹H NMR in DMSO: (M +H)⁺ = 583 A <1 4H-benzo[1,3]dioxin-6- 8.41 (brd, 1H, J = 4.69 Hz);ylmethoxy)-2-(4-fluoro- 8.06 (s, 1H); 7.94 (m, 2H); 7.87 (dd, phenyl)-6-1H, J = 8.21 & 2.34 Hz); 7.69 (s, (methanesulfonyl- 1H); 7.37 (m, 3H);7.19 (d, 1H, methyl-amino)- J = 8.79 Hz); 5.27 (s, 2H); 3.20 (s,benzofuran-3-carboxylic 3H); 2.95 (s, 3H); 2.84 (d, 3H, acid methylamideJ = 4.69 Hz); 1.72 (s, 6H) 330. 6-(Cyclopropylmethyl- ¹H NMR in DMSO:(M + H)⁺ = 447 A <1 methanesulfonyl-amino)- 8.44 (m, 1H); 7.94 (dd, J =5.9 & 2-(4-fluoro-phenyl)-5- 9.4 Hz, 2H); 7.62 (s, 1H); 7.38 (t,methoxy-benzofuran-3- J = 8.8 Hz, 2H); 7.20 (s, 1H); carboxylic acid3.90 (s, 3H); 3.44 (m, 2H); methylamide 2.92 (s, 3H); 2.84 (d, J = 4.7Hz, 3H); 0.87 (m, 1H); 0.35 (d, J = 1.7 Hz, 2H); 0.05 (m, 2H) 331.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 464 A <1(methanesulfonyl- 8.42 (m, 1H); 7.94 (dd, J = 5.9 &methylcarbamoylmethyl- 9.4 Hz, 2H); 7.90 (s, 1H); amino)-5-methoxy- 7.83(m, 1H); 7.38 (t, J = 8.8 Hz, 2H); benzofuran-3-carboxylic 7.20 (s, 1H);4.17 (s, 2H); acid methylamide 3.92 (s, 3H); 3.12 (s, 3H); 2.84 (d, J =4.7 Hz, 3H); 2.58 (d, J = 4.7 Hz, 3H) 332. 5-Fluoro-2-(4-fluoro- ¹H NMRin CDCl₃: (M + H)⁺ = 381 B <10 phenyl)-6- 7.89-7.85 (m, 2H); 7.87 (d, J= 6.3 Hz, methanesulfonylamino- 1H); 7.70 (d, J = 9.9 Hz,benzofuran-3-carboxylic 1H); 7.24-7.19 (m, 2H); acid methylamide 6.56(s, 1H); 5.74 (s, 1H); 3.04 (s, 1H); 2.99 (d, J = 4.8 Hz, 3H) 333.6-(Ethyl- ¹H NMR in CDCl₃: (M + H)⁺ = 409 A <10 methanesulfonyl-amino)-7.90-7.86 (m, 2H); 7.66 (d, J = 10.5 Hz, 5-fluoro-2-(4-fluoro- 1H); 7.57(d, J = 6.0 Hz, phenyl)-benzofuran-3- 1H); 7.24-7.18 (m, 2H); 5.74 (s,carboxylic acid 1H); 3.77 (q, J = 2.4 & 14.4 Hz, methylamide 2H);2.99-2.98 (m, 6H); 1.17 (t, J = 7.5 Hz, 3H) 334. 2-(4-Fluoro-phenyl)-6-¹H NMR in CDCl₃: (M + H)⁺ = 447 A <1 (1-methanesulfonyl- 7.85 (m, 2H);7.36 (s, 1H); pyrrolidin-3-yl)-5- 7.32 (s, 1H); 7.20 (m, 2H); 5.78 (brs,methoxy-benzofuran-3- 1H); 3.91 (s, 3H); 3.83 (m, 2H); carboxylic acid3.60 (m, 1H); 3.47 (m, 1H); methylamide 3.00 (d, J = 4.8 Hz, 3H); 2.87(s, 3H); 2.34 (m, 1H); 2.16 (m, 1H) 335. 5-Ethyl-2-(4-fluoro- ¹H NMR inDMSO: (M + H)⁺ = 449 A <1 phenyl)-6- 8.45 (m, 1H); 7.94 (dd, J = 5.3 &[methanesulfonyl-(2- 9.4 Hz, 2H); 7.78 (s, 1H); methoxy-ethyl)-amino]-7.56 (s, 1H); 7.39 (t, J = 8.8 Hz, 2H); benzofuran-3-carboxylic 3.32 (m,2H); 3.30 (s, 3H); acid methylamide 3.13 (s, 3H); 2.84 (d, J = 4.7 Hz,3H); 2.82 (q, J = 7.1 Hz, 2H); 1.24 (t, J = 7.1 Hz, 3H) 336.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 425 A <1methoxy-6-(3- 7.87 (dd, J = 7.0 and 5.1 Hz, 2H); methoxymethyl-5- 7.41(s, 1H); 7.40 (s, 1H); methyl-isoxazol-4-yl)- 7.20 (t, J = 8.8 Hz, 2H);5.81 (brs, 1H); benzofuran-3-carboxylic 4.45 (s, 2H); 3.86 (s, 3H); acidmethylamide 3.30 (s, 3H); 3.00 (d, J = 4.8 Hz, 3H); 2.35 (s, 3H) 337.5-Ethyl-6-[(2-fluoro- ¹H NMR in DMSO: (M + H)⁺ = 437 A <1ethyl)-methanesulfonyl- 8.47 (m, 1H); 7.94 (dd, J = 5.3 &amino]-2-(4-fluoro- 8.8 Hz, 2H); 7.84 (s, 1H); phenyl)-benzofuran-3-7.57 (s, 1H); 7.39 (t, J = 8.8 Hz, 2H); carboxylic acid 4.65-4.25 (m,2H, F-coupling); methylamide 3.98 (t, J = 4.1 Hz, 1H); 3.89 (t, J = 4.1Hz, 1H); 3.14 (s, 3H); 2.84 (d, J = 4.7 Hz, 3H); 2.82 (q, J = 7.6 Hz,2H) 1.24 (t, J = 7.6 Hz, 3H) 338. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO:(M + H)⁺ = 463.1 A <1 (methanesulfonyl-propyl- 8.40 (d, J = 4.7 Hz, 1H);7.90 (m, amino)-5-propoxy- 2H); 7.56 (s, 1H); 7.36 (t,benzofuran-3-carboxylic J = 8.2 Hz, 2H); 7.17 (s, 1H); acid methylamide4.04 (t, J = 6.5 Hz, 2H); 3.53 (s, 2H); 2.99 (s, 3H); 2.82 (d, J = 4.7Hz, 3H); 1.80 (m, 2H); 1.39 (m, 2H); 1.02 (t, J = 7.6 Hz, 3H); 0.85 (t,J = 4.1 Hz, 3H) 339. 5-Ethyl-2-(4-fluoro- ¹H NMR in CDCl₃: (M + H)⁺ =356.1 A <1 phenyl)-6-(1-hydroxy-1- 7.90 (m, 2H); 7.66 (s, 1H);methyl-ethyl)- 7.65 (s, 1H); 7.17 (m, 2H); 5.80 (brs,benzofuran-3-carboxylic 1H); 3.08 (q, J = 7.5 Hz, 2H); acid methylamide3.02 (d, J = 4.8 Hz, 3H); 1.73 (s, 6H); 1.33 (t, J = 7.5 Hz, 3H) 340.6-Acetyl-5-ethyl-2-(4- ¹H NMR in CDCl₃: (M + H)⁺ = 340.1 A <1fluoro-phenyl)- 7.95 (m, 2H); 7.80 (s, 1H); benzofuran-3-carboxylic 7.69(s, 1H); 7.19 (m, 2H); 5.82 (brs, acid methylamide 1H); 3.01 (d, J = 4.8Hz, 3H); 2.62 (s, 3H); 2.97 (q, J = 7.5 Hz, 2H); 1.22 (t, J = 7.5 Hz,3H) 341. 4-Chloro-6-ethylamino- ¹H NMR in DMSO: (M + H)⁺ = 363 B >1002-(4-fluoro-phenyl)-5- 9.82 (s, 1H); 8.38 (d, J = 4.4 Hz,hydroxy-benzofuran-3- 1H); 7.88 (dd, J = 8.8, 5.3 Hz, carboxylic acid2H); 7.35 (t, J = 8.8 Hz, 2H); methylamide 6.89 (s, 1H); 4.48 (t, J =7.0 Hz, 1H); 3.37 (q, J = 7.0 Hz, 2H); 2.80 (d, J = 4.4 Hz, 3H); 1.07(t, J = 7.0 Hz, 3H) 342. Methanesulfonic acid 4- ¹H NMR in DMSO: (M +H)⁺ = 441 A <10 chloro-6-ethylamino-2- 8.42 (d, J = 3.7 Hz, 1H); 7.90(dd, (4-fluoro-phenyl)-3- J = 8.8, 5.3 Hz, 2H); 7.46 (s, 1H);methylcarbamoyl- 7.37 (t, J = 8.8 Hz, 2H); 4.96 (t, benzofuran-5-ylester J = 6.8 Hz, 1H); 3.48 (s, 3H); 3.39 (pent, J = 7.0 Hz, 2H); 2.80(d, J = 3.7 Hz, 3H); 1.10 (t, J = 7.0 Hz, 2H) 343. 5-Ethyl-2-(4-fluoro-¹H NMR in DMSO: (M + H)⁺ = 488 A <1 phenyl)-6- 9.06 (d, J = 1.8 Hz, 1H);8.43 (m, (methanesulfonyl- 1H); 7.91 (dd, J = 5.3 & 8.8 Hz,thiazol-4-ylmethyl- 2H); 7.59 (s, 1H); 7.45 (m, 2H);amino)-benzofuran-3- 7.38 (t, J = 8.8 Hz, 2H); 5.01 (d, carboxylic acidJ = 4.9 Hz, 1H); 4.83 (d, J = 4.9 Hz, methylamide 1H); 3.14 (s, 3H);2.81 (d, J = 4.7 Hz, 3H); 2.65 (q, J = 7.6 Hz, 2H); 1.24 (t, J = 7.6 Hz,3H) 344. 6-(5-Cyclopropyl-3- ¹H NMR in CDCl₃: (M + H)⁺ = 451 A <1methoxymethyl-isoxazol- 7.87 (dd, J = 8.8 and 5.4 Hz, 2H);4-yl)-2-(4-fluoro- 7.46 (s, 1H); 7.41 (s, 1H); phenyl)-5-methoxy- 7.20(apparent t, J = 8.8 and 8.4 Hz, benzofuran-3-carboxylic 2H); 5.80 (brs,1H); 4.44 (s, acid methylamide 2H); 3.87 (s, 3H); 3.28 (s, 3H); 3.00 (d,J = 5.1 Hz, 3H); 1.92 (m, 1H); 1.13 (m, 2H); 0.97 (m, 2H) 345.6-(1-Acetyl-pyrrolidin-3- ¹H NMR in CDCl₃: (M + H)⁺ = 411 A <10yl)-2-(4-fluoro-phenyl)- 7.85 (m, 2H); 7.32 (m, 1H);5-methoxy-benzofuran-3- 7.25 (m, 3H); 5.77 (brs, 1H); carboxylic acid3.92 (s, 3H); 3.71-4.12 (m, 2H); methylamide 3.32-3.70 (m, 3H); 2.99 (d,J = 4.8 Hz, 3H); 2.18-2.39 (m, 2H); 2.10 (s, 3H) 346. 5-(3,4-Difluoro-¹H NMR in DMSO: (M + H)⁺ = 519.0 A <1 benzyloxy)-2-(4-fluoro- 8.39 (d, J= 4.4 Hz, 1H); 7.91 (m, phenyl)-6- 2H); 7.70 (s, 1H); 7.55-7.30 (m,(methanesulfonyl- 6H); 5.21 (s, 2H); 3.18 (s, 3H); methyl-amino)- 2.96(s, 3H); 2.82 (m, 3H) benzofuran-3-carboxylic acid methylamide 347.5-(2-Difluoromethoxy- ¹H NMR in CDCl₃: (M + H)⁺ = 549 A <1benzyloxy)-2-(4-fluoro- 7.86 (m, 2H); 7.57-7.42 (m, phenyl)-6- 3H);7.31-7.20 (m, 5H); 6.63 (t, (methanesulfonyl- 1H, J = 73.4 Hz); 5.74(brs, 1H); methyl-amino)- 5.24 (s, 2H); 3.28 (s, 3H);benzofuran-3-carboxylic 2.99 (d, 3H, J = 4.84 Hz); 2.81 (s, 3H) acidmethylamide 348. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 435 A<1 (methanesulfonyl- 8.39 (brd, 1H, J = 5.86); 7.92 (m, methyl-amino)-5-2H); 7.60 (s, 1H); 7.36 (t, 2H, propoxy-benzofuran-3- J = 8.79 Hz); 7.18(s, 1H); 4.04 (t, carboxylic acid 2H, J = 7.03); 3.20 (s, 3H);methylamide 3.02 (s, 3H); 2.82 (d, 3H, J = 4.10 Hz); 1.82 (m, 2H): 1.03(t, 3H, J = 7.03 Hz) 349. 5-Allyloxy-2-(4-fluoro- ¹H NMR in DMSO: (M +H)⁺ = 433 A <1 phenyl)-6- 8.37 (brm, 1H); 7.92 (m, 2H);(methanesulfonyl- 7.63 (s, 1H); 7.36 (t, 2H, methyl-amino)- J = 8.79Hz); 7.21 (s, 1H); benzofuran-3-carboxylic 6.18-6.06 (m, 1H); 5.47 (m,1H); acid methylamide 5.30 (m, 1H); 4.70 (d, 2H, J = 4.69 Hz); 3.20 (s,3H); 3.02 (s, 3H); 2.82 (d, 3H, J = 4.10 Hz) 350. 6-(5-Ethoxymethyl- ¹HNMR in CDCl₃: (M + H)⁺ = 425.21 A <1 isoxazol-3-yl)-2-(4- 8.03 (s, 1H);7.87 (dd, J = 5.28 & fluoro-phenyl)-5- 8.79 Hz, 2H); 7.45 (s, 1H);methoxy-benzofuran-3- 7.20 (t, J = 8.79 Hz, 2H); 6.82 (s, 1H);carboxylic acid 5.79 (brs, 1H); 4.64 (s, 2H); methylamide 3.96 (s, 3H);3.65 (q, J = 7.03 Hz, 2H); 3.00 (d, J = 4.84 Hz, 3H); 1.276 (t, J =7.03, 6.59 Hz, 3H) 351. 5-Cyclopropylmethoxy- ¹H NMR in DMSO: (M + H)⁺ =447 A <1 2-(4-fluoro-phenyl)-6- 8.38 (d, J = 4.4 Hz, 1H); 7.92 (m,(methanesulfonyl- 2H); 7.60 (s, 1H); 7.38 (t, methyl-amino)- J = 9.2 Hz,2H); 7.16 (s, 1H); benzofuran-3-carboxylic 3.95 (d, J = 7.0 Hz, 2H);3.25 (s, 3H); acid methylamide 3.08 (s, 3H); 2.83 (d, J = 4.4 Hz, 3H);1.20 (m, 1H); 0.62 (d, J = 7.0 Hz, 2H); 0.39 (d, J = 5.3 Hz, 2H) 352.5-(3,5-Dimethoxy- ¹H NMR in DMSO: (M + H)⁺ = 543 A <1benzyloxy)-2-(4-fluoro- 8.39 (brd, 1H, J = 4.69); 7.93 (m, phenyl)-6-2H); 7.71 (s, 1H); 7.38 (t, 2H, (methanesulfonyl- J = 8.79); 7.31 (s,1H); 6.72 (d, methyl-amino)- 2H, J = 2.34); 6.46 (m, 1H);benzofuran-3-carboxylic 5.17 (s, 2H); 3.75 (s, 6H); 3.22 (s, acidmethylamide 3H); 3.00 (s, 3H); 2.83 (d, 3H, J = 4.69 Hz) 353.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M − H)⁻ = 559 A <1(4-methanesulfonyl- 8.39 (brd, 1H, J = 4.40 Hz); benzyloxy)-6- 7.98-7.89(m, 4H); 7.80 (d, 2H, (methanesulfonyl- J = 8.4 Hz); 7.71 (s, 1H); 7.37(m, methyl-amino)- 3H); 5.36 (s, 2H); 3.28 (s, 3H);benzofuran-3-carboxylic 3.22 (s, 3H); 2.98 (s, 3H); acid methylamide2.81 (d, 3H, J = 4.40 Hz) 354. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃:(M + H)⁺ = 437.22 B <10 hydroxy-6- 8.15 (s, 1H); 7.93 (m, 2H);[methanesulfonyl-(2-oxo- 7.39 (s, 1H); 7.15 (t, J = 2.5 Hz, 2H);propyl)-amino]- 5.79 (s, 1H); 4.54 (s, 1H); benzofuran-3-carboxylic 4.49(s, 1H); 3.34 (s, 3H); 3.24 (s, acid methylamide 1H); 3.19 (s, 1H); 1.79(s, 2H) 355. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 541 A <1(methanesulfonyl- 8.36 (d, J = 4.8 Hz, 1H); 8.04 (d,methyl-amino)-5-[2-(4- J = 8.79 Hz, 2H); 7.90 (m, 2H);methoxy-phenyl)-2-oxo- 7.60 (s, 1H); 7.36 (t, J = 8.79 Hz,ethoxy]-benzofuran-3- 2H); 7.28 (s, 1H); 7.08 (d, carboxylic acid J =9.35 Hz, 2H); 5.67 (s, 2H); methylamide 3.86 (s, 3H); 3.29 (s, 3H); 3.07(s, 3H); 2.77 (d, J = 4.41 Hz, 3H) 356. 5-(3-Cyano-benzyloxy)- ¹H NMR inDMSO: (M − H)⁻ = 506 A <1 2-(4-fluoro-phenyl)-6- 8.39 (brd, 1H, J = 4.69Hz); (methanesulfonyl- 8.00 (s, 1H); 7-94-7.81 (m, 3H); methyl-amino)-7.72 (s, 1H); 7.64 (t, 2H, J = 7.62 Hz); benzofuran-3-carboxylic 7.37(t, 2H, J = 8.79 Hz); 7.30 (s, acid methylamide 1H); 5.29 (s, 2H); 3.19(s, 3H); 2.97 (s, 3H); 2.82 (d, 3H, J = 4.69 Hz) 357.5-(4-Cyano-benzyloxy)- ¹H NMR in DMSO: (M + H)⁺ = 508 A <12-(4-fluoro-phenyl)-6- 8.37 (brd, 1H, J = 4.84 Hz); (methanesulfonyl-7.90 (m, 4H); 7.72 (m, 3H); 7.37 (t, methyl-amino)- 2H, J = 8.79 Hz);7.30 (s, 1H); benzofuran-3-carboxylic 5.33 (s, 2H); 3.21 (s, 3H); acidmethylamide 2.97 (s, 3H); 2.81 (d, 3H, J = 4.0 Hz) 358.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 366 A <1methoxy-6-(2H- 8.49 (s, 1H); 8.05 (s, 1H); GCMS [1,2,4]triazol-3-yl)-7.86-7.91 (m, 2H); 7.58 (s, 1H); benzofuran-3-carboxylic 7.20-7.26 (m,2H); 5.82 (brs, 1H); acid methylamide 4.15 (s, 3H); 3.00-3.02 (d, 3H, J= 5.28 Hz) 359. 4-{2-[2-(4-Fluoro- ¹H NMR in DMSO: (M − H)⁻ = 596 A <10phenyl)-6- 10.37 (s, 1H); 8.39 (brd, 1H, (methanesulfonyl- J = 4.84 Hz);7.91 (m, 4H); methyl-amino)-3- 7.75 (d, 2H, J = 8.35 Hz); 7.70 (s, 1H);methylcarbamoyl- 7.37 (t, 2H, J = 8.79 Hz); 7.20 (s,benzofuran-5-yloxy]- 1H); 4.93 (s, 2H); 4.28 (q, 2H,acetylamino}-benzoic J = 7.03 Hz); 3.28 (s, 3H); 3.14 (s, acid ethylester 3H); 2.78 (d, 3H, J = 4.40 Hz); 1.30 (t, 3H, J = 7.03 Hz) 360.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M − H)⁻ = 527 A <1[2-(4-fluoro-phenyl)-2- 8.38 (brd, 1H, J = 5.28 Hz); oxo-ethoxy]-6- 8.17(m, 2H); 7.90 (m, 2H); 7.62 (s, (methanesulfonyl- 1H); 7.45-7.31 (m,5H); 5.73 (s, methyl-amino)- 2H); 3.29 (s, 3H); 3.06 (s, 3H);benzofuran-3-carboxylic 2.78 (d, 3H, J = 4.69 Hz) acid methylamide 361.6-(Benzyl- ¹H NMR in DMSO: (M + H)⁺ = 511 A <1 methanesulfonyl-amino)-8.38 (brd, 1H, J = 4.69 Hz); 2-(4-fluoro-phenyl)-5- 7.86 (m, 2H); 7.33(t, 2H, J = 8.79 Hz); isopropoxy-benzofuran- 7.28-7.16 (m, 6H); 7.10 (s,1H); 3-carboxylic acid 4.80 (brm, 3H); 3.11 (s, 3H); methylamide 2.79(d, 3H, J = 4.69 Hz); 1.38 (d, 6H, J = 5.86 Hz) 362. 4-Chloro-6-(ethyl-¹H NMR in DMSO: (M + H)⁺ = 391.0 A <10 methyl-amino)-2-(4- 8.38 (d, J =4.4 Hz, 1H); 7.90 (m, fluoro-phenyl)-5- 2H); 7.36 (t, J = 8.4 Hz, 2H);methoxy-benzofuran-3- 7.05 (s, 1H); 3.86 (s, 3H); 3.09 (q, carboxylicacid J = 7.03 Hz, 2H); 2.81 (d, methylamide J = 4.4 Hz, 3H); 2.75 (s,3H); 0.93 (t, J = 7.1 Hz, 3H) 363. 4-Chloro-6-ethylamino- ¹H NMR inDMSO: (M + H)⁺ = 377.0 A <1 2-(4-fluoro-phenyl)-5- 8.34 (d, J = 4.8 Hz,1H); 7.86 (m, methoxy-benzofuran-3- 2H); 7.33 (t, J = 9.2 Hz, 2H);carboxylic acid 6.99 (s, 1H); 4.67 (t, J = 6.6 Hz, 1H); methylamide 3.89(s, 3H); 3.38 (q, J = 7.04 Hz, 2H); 2.80 (d, J = 4.4 Hz, 3H); 1.07 (t, J= 7.0 Hz, 3H) 364. 6-Ethylamino-2-(4- ¹H NMR in DMSO: (M + H)⁺ = 329B >30 fluoro-phenyl)-5- 8.20 (d, J = 4.7 Hz, 1H); 7.88 (dd,hydroxy-benzofuran-3- J = 8.8, 5.3 Hz, 2H); 7.29 (t, carboxylic acid J =8.8 Hz, 2H); 6.83 (s, 1H); methylamide 6.66 (s, 1H); 4.83 (t, J = 5.0Hz, 1H); 3.11 (m, 2H); 2.79 (d, J = 4.7 Hz, 3H); 1.19 (t, J = 7.0 Hz,3H) 365. 5-(3-Bromo-propoxy)-6- ¹H NMR in DMSO: (M + H)⁺ = 499, A <1ethylamino-2-(4-fluoro- 8.30 (d, J = 4.7 Hz, 1H); 7.86 (dd, 451phenyl)-benzofuran-3- J = 8.8, 5.3 Hz, 2H); 7.30 (t, carboxylic acid J =8.8 Hz, 2H); 6.93 (s, 1H); methylamide 6.75 (s, 1H); 5.20 (t, J = 5.0Hz, 1H); 4.14 (t, J = 4.8 Hz, 2H); 3.78 (t, J = 6.7 Hz, 2H); 3.20 (m,2H); 2.81 (d, J = 4.7 Hz, 3H); 2.36 (m, 2H); 1.23 (t, J = 7.0 Hz, 3H)366. 5-Allyloxy-6- ¹H NMR in DMSO: (M + H)⁺ = 369 A <1ethylamino-2-(4-fluoro- 8.20 (d, J = 4.7 Hz, 1H); 7.80 (dd,phenyl)-benzofuran-3- J = 8.8, 5.3 Hz, 2H); 7.31 (t, carboxylic acid J =8.8 Hz, 2H); 6.93 (s, 1H); methylamide 6.74 (s, 1H); 6.10 (m, 1H); 5.50(m, 1H); 5.30 (m, 1H); 5.00 (t, J = 5.0 Hz, 1H); 4.60 (m, 2H); 3.18 (m,2H); 2.80 (d, J = 4.7 Hz, 2H); 1.20 (t, J = 7.0 Hz, 3H) 367.5-(3-Ethoxy-propoxy)-6- ¹H NMR in DMSO: (M + H)⁺ = 415 A <1ethylamino-2-(4-fluoro- 8.20 (d, J = 4.4 Hz, 1H); 7.80 (dd,phenyl)-benzofuran-3- J = 8.8, 5.3 Hz, 2H); 7.31 (t, carboxylic acid J =8.8 Hz, 2H); 6.90 (s, 1H); methylamide 6.72 (s, 1H); 5.01 (t, J = 5.7Hz, 1H); 4.07 (t, J = 6.5 Hz, 2H); 3.56 (t, J = 6.4 Hz, 2H); 3.42 (q, J= 7.0 Hz, 2H); 3.20 (m, 2H); 2.80 (d, J = 4.4 Hz, 3H); 2.00 (t, J = 6.5Hz, 2H); 1.20 (t, J = 7.0 Hz, 3H); 1.10 (t, J = 7.0 Hz, 3H) 368.2-[2-(4-Fluoro-phenyl)- ¹H NMR in CDCl₃: (M + H)⁺ = 412 A <15-methoxy-3- 7.83 (m, 2H); 7.15 (s, 1H); methylcarbamoyl- 7.14 (s, 1H);7.10 (m, 2H); 5.76 (brs, benzofuran-6-yl]- 1H); 5.18 (d, J = 8.353 Hz,1H); pyrrolidine-1-carboxylic 4.25 (s, 2H); 3.93 (s, 3H); acid amide3.72 (m, 2H); 2.99 (d, J = 4.836 Hz, 3H); 1.89 (m, 2H); 1.25 (s, 2H)369. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M − H)⁻ = 447 A <1(methanesulfonyl- 8.38 (brd, 1H, J = 4.69 Hz); methyl-amino)-5-(2-oxo-7.90 (m, 2H); 7.62 (s, 1H); 7.36 (t, propoxy)-benzofuran-3- 2H, J = 8.79Hz); 7.12 (s, 1H); carboxylic acid 4.97 (s, 2H); 3.24 (s, 3H);methylamide 3.04 (s, 3H); 2.81 (d, 3H, J = 4.10 Hz); 2.20 (s, 3H) 370.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M − H)⁻ = 449 A <1(2-hydroxy-propoxy)-6- 8.41 (brd, 1H, J = 4.69 Hz); (methanesulfonyl-7.94 (m, 2H); 7.60 (s, 1H); 7.38 (t, methyl-amino)- 2H, J = 8.79 Hz);7.20 (s, 1H); benzofuran-3-carboxylic 4.87 (d, 1H, J = 4.69 Hz); 4.06(m, acid methylamide 1H); 3.96 (m, 2H); 3.24 (s, 3H); 3.06 (s, 3H); 2.84(d, 3H, J = 4.69 Hz); 1.22 (d, 3H, J = 5.86) 371. 2-(4-Fluoro-phenyl)-6-¹H NMR in DMSO: (M + H)⁺ = 489 A <1 (methanesulfonyl- 8.44 (brd, 1H, J =4.10 Hz); methyl-amino)-5-(1- 7.94 (m, 2H); 7.76 (s, 1H); 7.48 (s,methyl-1H-tetrazol-5- 1H); 7.40 (t, 2H, J = 8.79);ylmethoxy)-benzofuran- 5.65 (s, 2H); 4.18 (s, 3H); 3.18 (s, 3-carboxylicacid 3H); 3.02 (s, 3H); 2.86 (d, 3H, methylamide J = 4.10 Hz) 372.2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ = 439 A <1(5-isopropoxymethyl- 7.96 (s, 1H); 7.85 (dd, J = 5.28 &isoxazol-3-yl)-5- 8.79 Hz, 2H); 7.40 (s, 1H); methoxy-benzofuran-3- 7.18(t, J = 8.35& 8.79 Hz, 2H); carboxylic acid 6.78 (s, 1H); 5.98 (brs,1H); 4.64 (s, methylamide 2H); 3.94 (s, 3H); 3.78 (septet, J = 6.15 Hz,1H); 3.01 (d, J = 4.83 Hz, 3H); 1.25 (d, J = 6.15 Hz, 6H) 373.5-(5-Diethylamino- ¹H NMR in DMSO: (M + H)⁺ = 562 A <1[1,2,4]thiadiazol-3- 8.38 (brd, 1H, J = 4.40 Hz);ylmethoxy)-2-(4-fluoro- 7.94 (m, 2H); 7.61 (s, 1H); 7.37 (m, phenyl)-6-3H); 5.22 (s, 2H); 3.47 (brm, (methanesulfonyl- 4H); 3.28 (s, 3H); 3.08(s, 3H); methyl-amino)- 2.84 (d, 3H, J = 4.84 Hz); 1.18 (t,benzofuran-3-carboxylic 6H, J = 7.03 Hz) acid methylamide 374. 5-[5- ¹HNMR in DMSO: (M + H)⁺ = 560 A <1 (Cyclopropylmethyl- 8.60 (brm, 1H);8.38 (brd, 1H, amino)-[1,2,4]thiadiazol- J = 4.10 Hz); 7.94 (m, 2H);3-ylmethoxy]-2-(4- 7.61 (s, 1H); 7.38 (m, 3H); 5.19 (brs,fluoro-phenyl)-6- 2H); 3.26 (s, 3H); 3.18 (t, 2H, (methanesulfonyl- J =5.86 Hz); 3.07 (s, 3H); 2.84 (d, methyl-amino)- 3H, J = 4.69 Hz); 1.10(m, 1H); benzofuran-3-carboxylic 0.48 (m, 2H); 0.24 (m, 2H) acidmethylamide 375. 6-(2-Amino-1-hydroxy- ¹H NMR in CDCl₃: (M + H)⁺ = 401.1B <30 1-methyl-ethyl)-2-(4- 7.85 (m, 2H); 7.71 (s, 1H);fluoro-phenyl)-5- 7.19 (s, 1H); 7.16 (m, 2H); 6.35 (brs,isopropoxy-benzofuran- 1H); 4.76 (m, 1H); 4.60 (brs, 3-carboxylic acid2H); 3.48 (m, 2H); 2.99 (d, methylamide J = 4.69 Hz, 3H); 1.47 (s, 3H);1.40 (d, J = 5.86 Hz, 3H); 1.37 (d, J = 5.86 Hz, 3H) 376.6-(1-Amino-1-methyl- ¹H NMR in CDCl₃: (M + H)⁺ = 386 A <1ethyl)-2-(4-fluoro- 7.84 (m, 2H); 7.49 (s, 1H); phenyl)-5-isopropoxy-7.37 (s, 1H); 7.26 (m, 2H); 5.74 (brs, benzofuran-3-carboxylic 1H); 4.84(septet, J = 6.15 Hz, acid methylamide 1H); dd 4.53 (brs, 2H); 2.99 (d,J = 2.64 Hz, 3H); 1.67 (s, 6H); 1.47 (d, J = 6.16 Hz, 6H) 377.2-[2-(4-Fluoro-phenyl)- ¹H NMR in CDCl₃: (M + H)⁺ = 426 A <105-methoxy-3- 7.85 (m, 2H); 7.34 (s, 1H); methylcarbamoyl- 7.30 (s, 1H);7.18 (m, 2H); 5.77 (s, benzofuran-6-yl]- 1H); 4.03 (d, J = 4.39 Hz, 1H);pyrrolidine-1-carboxylic 3.94 (s, 3H); 3.71 (m, 2H); acid methylamide2.99 (d, J = 1.32 Hz, 3H); 2.71 (d, J = 1.32 Hz, 3H); 2.38 (m, 1H); 1.86(m, 3H) 378. 6-(3,5-Dimethyl- ¹H NMR in DMSO: (M + H)⁺ = 409 A <1isoxazol-4-yl)-2-(4- 8.53 (s, 1H); 7.94-7.99 (m, 2H); fluoro-phenyl)-5-7.61 (s, 1H); 7.37-7.43 (t, 2H, methoxy-benzofuran-3- J = 9.38 Hz); 7.22(s, 1H); 3.85 (s, carboxylic acid 3H) 3.36-3.40 (t, 2H, ethylamide J =5.86 Hz); 2.31 (s, 3H); 2.12 (s, 3H); 1.16-1.20 (t, 3H, J = 5.28 Hz)379. 6-(3,5-Dimethyl- ¹H NMR in DMSO: (M + H)⁺ = 423 B >30isoxazol-4-yl)-2-(4- 8.42-8.45 (d, 1H, J = 8.21 Hz); fluoro-phenyl)-5-7.93-7.98 (m, 2H), 7.59 (s, 1H); methoxy-benzofuran-3- 7.37-7.42 (t, 2H,J = 8.79 Hz); carboxylic acid 7.18 (s, 1H); 4.18-4.24 (septet,isopropylamide 1H, J = 7.03 Hz); 3.83 (s, 3H); 2.30 (s, 3H); 2.11 (s,3H); 1.19-1.21 (d, 6H, J = 7.03 Hz) 380. 6-(3,5-Dimethyl- ¹H NMR inDMSO: (M + H)⁺ = 421 A <1 isoxazol-4-yl)-2-(4- 8.59-8.61 (d, 1H, J =4.10 Hz); fluoro-phenyl)-5- 7.90-7.94 (m, 2H); 7.95 (s, 1H);methoxy-benzofuran-3- 7.36-7.42 (t, 2H, J = 8.79 Hz); carboxylic acid7.16 (s, 1H); 3.83 (s, 3H); cyclopropylamide 2.93-2.99 (m, 1H); 2.29 (s,3H); 2.10 (s, 3H); 0.71-0.77 (m, 2H); 0.54-0.60 (m, 2H) 381.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 427.1 A <1isopropoxy-6-(5-methyl- 7.85 (m, 2H); 7.77 (s, 1H);2-oxo-oxazolidin-5-yl)- 7.35 (s, 1H); 7.19 (m, 2H); 5.74 (brs,benzofuran-3-carboxylic 1H); 5.03 (brs, 1H); 4.76 (m, acid methylamide1H); 3.78 (dd, J = 2.2 & 8.4 Hz, 2H); 2.97 (d, J = 5.2 Hz, 3H); 1.82 (s,3H); 1.40 (d, J = 5.2 Hz, 3H); 1.37 (d, J = 5.2 Hz, 3H) 382.[2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H₂O)⁺ = 524 A <1(methanesulfonyl- 8.38 (brd, 1H, J = 4.69 Hz); methyl-amino)-3- 7.93 (m,2H); 7.63 (s, 1H); 7.38 (t, methylcarbamoyl- 2H, J = 8.79 Hz); 7.10 (s,1H); benzofuran-5-yloxy]- 4.82 (s, 2H); 3.26 (s, 3H); acetic acidtert-butyl 3.07 (s, 3H); 2.82 (d, 3H, J = 4.69 Hz); ester 1.46 (s, 9H)383. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 381 B <10methoxy-6-(5-methyl- 13.42 (s, 1H), 8.44-8.46 (d, 1H,2H-[1,2,4]triazol-3-yl)- J = 4.69 Hz); 8.25 (s, 1H);benzofuran-3-carboxylic 7.94-7.99 (m, 2H); 7.36-7.42 (t, 2H, acidmethylamide J = 8.79 Hz); 7.27 (s, 1H); 4.02 (s, 3H); 2.85-2.86 (d, 3H,J = 4.69 Hz); 2.34 (s, 3H) 384. 6-(1-Amino-1-methyl- ¹H NMR in CDCl₃:(M + H—NH₂)⁺ = 340 B <30 ethyl)-2-(4-fluoro- 7.84 (m, 2H); 7.51 (s, 1H);phenyl)-5-methoxy- 7.32 (s, 1H); 7.17 (m, 2H); 5.84 (brs,benzofuran-3-carboxylic 1H); 3.95 (s, 3H); 2.97 (d, acid methylamide J =4.84 Hz, 3H); 2.19 (brs, 2H); 1.59 (s, 6H) 385. 6-(1-Acetylamino-1- ¹HNMR in CDCl₃: (M + H—NHAc)⁺ = 340 A <1 methyl-ethyl)-2-(4- 7.84 (m, 2H);7.52 (s, 1H); fluoro-phenyl)-5- 7.31 (s, 1H); 7.15 (m, 2H); 6.03 (brs,methoxy-benzofuran-3- 1H); 5.76 (brs, 1H); 3.92 (s, carboxylic acid 3H);2.96 (d, J = 4.84 Hz, 3H); methylamide 1.92 (s, 3H); 1.80 (s, 6H) 386.[2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M − H)⁻ = 449 A <30(methanesulfonyl- 8.39 (brd, 1H, J = 4.69 Hz); methyl-amino)-3- 7.93 (m,2H); 7.62 (s, 1H); 7.38 (t, methylcarbamoyl- 2H, J = 8.79 Hz); 7.17 (s,1H); benzofuran-5-yloxy]- 4.86 (s, 2H); 3.26 (s, 3H); acetic acid 3.06(s, 3H); 2.83 (d, 3H, J = 4.69 Hz) 387. 6-(2,5-Dimethyl-2H- ¹H NMR inDMSO: (M + H)⁺ = 395 B <10 [1,2,4]triazol-3-yl)-2-(4- 8.45-8.47 (d, 1H,J = 4.69 Hz); fluoro-phenyl)-5- 7.93-7.98 (m, 2H); 7.69 (s, 1H);methoxy-benzofuran-3- 7.36-7.42 (t, 2H, J = 8.79 Hz); carboxylic acid7.29 (s, 1H); 3.88 (s, 3H); methylamide 3.60 (s, 3H); 2.85-2.86 (d, 3H,J = 4.10 Hz); 2.28 (s, 3H) 388. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO:(M + H)⁺ = 490 A <1 (methanesulfonyl- 8.40 (brm, 1H); 7.95 (m, 2H);methyl-amino)-5- 7.89 (d, 1H, J = 2.93 Hz); 7.82 (d,(thiazol-2-ylmethoxy)- 1H, J = 2.93); 7.70 (s, 1H);benzofuran-3-carboxylic 7.40 (m, 3H); 5.60 (s, 2H); 3.25 (s, acidmethylamide 3H); 3.02 (s, 3H); 2.85 (d, 3H, J = 4.69 Hz) 389.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 412 A <10methoxy-6-(4-methyl- 10.59 (brs, 1H); 8.37 (m, 1H);2,5-dioxo-imidazolidin- 7.96 (s, 1H); 7.94 (m, 2H); 4-yl)-benzofuran-3-7.71 (s, 1H); 7.39 (m, 2H); carboxylic acid 7.15 (s, 1H); 3.77 (s, 3H);2.82 (d, methylamide J = 4.8 Hz, 3H); 1.71 (s, 3H) 390.2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H—NH—SO₂Me)⁺ = 340 A <10(1- 7.84 (m, 2H); 7.51 (s, 1H); methanesulfonylamino-1- 7.44 (s, 1H);7.19 (m, 2H); 5.88 (s, methyl-ethyl)-5- 1H); 5.79 (brs, 1H); 4.00 (s,methoxy-benzofuran-3- 3H); 2.98 (d, J = 4.84 Hz, 3H); carboxylic acid2.52 (s, 3H); 1.82 (s, 6H) methylamide 391. 5-(6-Bromomethyl- ¹H NMR inDMSO: (M + H)⁺ = 746 A <10 pyridin-2-ylmethoxy)-6- 8.38 (d, J = 4.8 Hz,1H); 7.90 (m, [(6-bromomethyl- 3H); 7.73 (t, J = 7.1 Hz, 1H);pyridin-2-ylmethyl)- 7.64 (s, 1H); 7.60 (d, J = 7.5 Hz, 1H);methanesulfonyl-amino]- 7.53 (d, J = 7.5 Hz, 1H); 7.48 (d,2-(4-fluoro-phenyl)- J = 7.5 Hz, 1H); 7.37 (m, 3H);benzofuran-3-carboxylic 7.31 (s, 1H); 5.33 (s, 2H); acid methylamide4.98 (s, 2H); 4.72 (s, 2H); 4.61 (s, 2H); 3.18 (s, 3H); 2.81 (d, J = 4.8Hz, 3H) 392. 2-[2-(4-Fluoro-phenyl)- ¹H NMR in DMSO: (M + H)⁺ = 562 A <16-(methanesulfonyl- 8.60 (s, 1H); 8.40 (brd, 1H, methyl-amino)-3- J =4.69 Hz); 7.95 (m, 2H); methylcarbamoyl- 7.73 (s, 1H); 7.40 (m, 3H);5.63 (s, benzofuran-5- 2H); 4.32 (q, 2H, J = 7.03 Hz);yloxymethyl]-thiazole-4- 3.27 (s, 3H); 3.06 (s, 3H); carboxylic acidethyl 2.84 (d, 3H, J = 4.69 Hz); 1.32 (t, 3H, ester J = 7.03) 393.2-[2-(4-Fluoro-phenyl)- ¹H NMR in DMSO: (M − H)⁻ = 532 A >306-(methanesulfonyl- 8.52 (s, 1H); 8.41 (brd, 1H, methyl-amino)-3- J =4.69 Hz); 7.95 (m, 2H); methylcarbamoyl- 7.73 (s, 1H); 7.40 (m, 3H);5.61 (s, benzofuran-5- 2H); 3.26 (s, 3H); 3.06 (s, 3H);yloxymethyl]-thiazole-4- 2.85 (d, 3H, J = 4.69 Hz) carboxylic acid 394.6-Dimethylamino-2-(4- ¹H NMR in CDCl₃: (M + H)⁺ = 343 A <1fluoro-phenyl)-5- 7.85 (dd, J = 8.8 & 5.3 Hz, 2H); methoxy-benzofuran-3-7.26 (s, 1H); 7.17 (t, J = 8.8 Hz, carboxylic acid 2H); 7.14 (s, 1H);5.80 (brs, methylamide 1H); 3.96 (s, 3H); 2.98 (d, J = 4.8 Hz, 3H); 2.84(s, 6H) 395. 5-Cyanomethoxy-2-(4- ¹H NMR in DMSO: (M + H)⁺ = 432; A <1fluoro-phenyl)-6- 8.44 (brd, 1H, J = 4.10 Hz); (methanesulfonyl- 7.93(m, 2H); 7.77 (s, 1H); 7.41 (m, methyl-amino)- 3H); 5.32 (s, 2H); 3.22(s, 3H); benzofuran-3-carboxylic 3.08 (s, 3H); 2.84 (d, 3H, acidmethylamide J = 4.69 Hz) 396. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO:(M + H)⁺ = 488 A <1 (methanesulfonyl- 8.40 (brd, 1H, J = 4.69 Hz);methyl-amino)-5-(5- 7.95 (m, 2H); 7.68 (s, 1H), 7.38 (m,methyl-isoxazol-3- 3H); 6.40 (s, 1H); 5.30 (s, 2H);ylmethoxy)-benzofuran- 3.21 (s, 3H); 3.00 (s, 3H); 3-carboxylic acid2.84 (d, 3H, J = 4.10 Hz); 2.44 (s, 3H) methylamide 397. 5-(5-Chloro- ¹HNMR in DMSO: (M + H)⁺ = 525 A <1 [1,2,3]thiadiazol-4- 8.46 (brd, 1H, J =4.10 Hz); ylmethoxy)-2-(4-fluoro- 7.98 (m, 2H); 7.69 (s, 1H); 7.51 (s,phenyl)-6- 1H); 7.40 (t, 2H, J = 8.79 Hz); (methanesulfonyl- 5.66 (s,2H); 3.17 (s, 3H); methyl-amino)- 2.95 (s, 3H); 2.87 (d, 3H, J = 4.69Hz) benzofuran-3-carboxylic acid methylamide 398. 2-(4-Fluoro-phenyl)-6-¹H NMR in DMSO: (M + H)⁺ = 487 A <1 (methanesulfonyl- 8.42 (brd, 1H, J =4.69); 7.98 (m, methyl-amino)-5-(1- 2H); 7.70 (s, 1H); 7.52 (s, 1H);methyl-1H-imidazol-2- 7.39 (t, 2H, J = 8.79); 7.21 (s,ylmethoxy)-benzofuran- 1H); 6.91 (s, 1H); 5.27 (s, 2H); 3-carboxylicacid 3.74 (s, 3H); 3.15 (s, 3H); methylamide 2.94 (s, 3H); 2.87 (d, 3H,J = 4.69 Hz) 399. 5-(1-Benzyl-1H- ¹H NMR in DMSO: (M + H)⁺ = 563 A ***imidazol-2-ylmethoxy)- 8.42 (brm, 1H); 7.95 (m, 2H);2-(4-fluoro-phenyl)-6- 7.68 (s, 1H); 7.51 (s, 1H); (methanesulfonyl-7.42-7.20 (m, 8H); 7.00 (s, 1H); methyl-amino)- 5.38 (s, 2H); 5.25 (s,2H); 3.04 (s, benzofuran-3-carboxylic 3H); 2.91 (s, 3H); 2.86 (d, 3H,acid methylamide J = 4.10 Hz) 400. 2-(2,4-Difluoro-phenyl)- ¹H NMR inDMSO: (M + H)⁺ = 413 A *** 6-(3,5-dimethyl-isoxazol- 8.10-8.12, (d, 1H,J = 4.69 Hz); 4-yl)-5-methoxy- 7.78-7.86 (q, 1H, J = 6.45 Hz);benzofuran-3-carboxylic 7.61 (s, 1H); 7.42-7.49 (m, 1H); acidmethylamide 7.33 (s, 1H); 7.27-7.32 (m, 1H); 3.85 (s, 3H); 2.77-2.78 (d,3H, J = 4.69 Hz); 2.29 (s, 3H); 2.10 (s, 3H) 401. 6-(3,5-Dimethyl- ¹HNMR in DMSO: (M + H)⁺ = 478 A <1 isoxazol-4-yl)-2-(4- 9.13 (d, 1H, J =1.17 Hz); fluoro-phenyl)-5- 8.41-8.43 (d, 1H, J = 4.69 Hz);(thiazol-4-ylmethoxy)- 7.94-7.99 (m, 2H); 7.64-7.65 (d, 1H,benzofuran-3-carboxylic J = 1.17 Hz); 7.61 (s, 1H); acid methylamide7.45 (s, 1H); 7.36-7.42 (t, 2H, J = 8.79 Hz); 5.28 (s, 2H); 2.86-2.88(d, 3H, J = 4.69 Hz); 2.29 (s, 3H); 2.11 (s, 3H) 402. 5-(5-Amino-4H- ¹HNMR in DMSO: (M + H)⁺ = 489 A <1 [1,2,4]triazol-3- 11.94 (brs, 1H); 8.36(brd, 1H, ylmethoxy)-2-(4-fluoro- J = 4.69 Hz); 7.93 (m, 2H); phenyl)-6-7.57 (s, 1H); 7.36 (m, 3H); 5.96 (brs, (methanesulfonyl- 2H); 5.01 (s,2H); 3.19 (s, 3H); methyl-amino)- 2.99 (s, 3H); 2.83 (d, 3H,benzofuran-3-carboxylic J = 4.10 Hz) acid methylamide 403.5-(4-Chloro-1-methyl- ¹H NMR in DMSO: (M + H)⁺ = 521 A <1 1H-pyrazol-3-8.44 (brd, 1H, J = 4.69 Hz); ylmethoxy)-2-(4-fluoro- 7.96 (m, 3H); 7.62(s, 1H); 7.47 (s, phenyl)-6- 1H); 7.38 (t, 2H, J = 8.79 Hz);(methanesulfonyl- 5.16 (s, 2H); 3.84 (s, 3H); methyl-amino)- 3.16 (s,3H); 2.93 (s, 3H); 2.86 (d, benzofuran-3-carboxylic 3H, J = 4.69 Hz)acid methylamide 404. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ =487 A <1 (methanesulfonyl- 8.42 (brm, 1H); 7.97-7.90 (m,methyl-amino)-5-(2- 3H); 7.56 (s, 1H); 7.47 (s, 1H);pyrazol-1-yl-ethoxy)- 7.38 (t, 2H, J = 8.79); 7.23 (s,benzofuran-3-carboxylic 1H); 6.27 (m, 1H); 4.60 (brm, acid methylamide2H); 4.54 (brm, 2H); 2.99 (s, 3H); 2.84 (m, 6H) 405.2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M + H)⁺ = 473 A <1(1H-imidazol-2- 12.24 (brs, 1H); 8.41 (brd, 1H, ylmethoxy)-6- J = 4.10Hz); 7.95 (m, 2H); (methanesulfonyl- 7.63 (s, 1H); 7.47 (s, 1H); 7.39(t, 2H, methyl-amino)- J = 8.79 Hz); 7.19 (s, 1H); 6.95 (s,benzofuran-3-carboxylic 1H); 5.20 (s, 2H); 3.16 (s, 3H); acidmethylamide 2.91 (s, 3H); 2.86 (d, 3H, J = 4.69 Hz) 406. 6-(2,5-Dioxo-¹H NMR in DMSO: (M + H)⁺ = 398 B <10 imidazolidin-4-yl)-2-(4- 8.38 (m,1H); 8.08 (s, 1H); fluoro-phenyl)-5- 7.93 (m, 2H); 7.56 (s, 1H); 7.34(m, methoxy-benzofuran-3- 2H); 7.15 (s, 1H); 5.29 (s, 1H); carboxylicacid 3.90 (s, 1H); 3.80 (s, 3H); 2.82 (d, methylamide J = 3.6 Hz, 3H)407. 5-(3,5-Dimethyl- ¹H NMR in DMSO: (M − H)⁻ = 456.0 *** <10isoxazol-4-yl)-2-(4- 9.18 (brs, 1H); 8.37 (d, fluoro-phenyl)-6- J = 2.20Hz, 1H); 7.98-7.93 (m, methanesulfonylamino- 2H); 7.72 (s, 1H);7.41-7.34 (m, benzofuran-3-carboxylic 3H); 3.01 (s, 3H); 2.79 (d, acidmethylamide J = 4.84 Hz, 3H); 2.22 (s, 3H); 2.04 (s, 3H) 408.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 504 *** <1(methanesulfonyl- 8.33 (brd, 1H, J = 4.10); 7.92 (m, methyl-amino)-5-(1-2H); 7.84 (d, 1H, J = 2.93 Hz); thiazol-2-yl-ethoxy)- 7.75 (d, 1H, J =2.93); 7.66 (s, benzofuran-3-carboxylic 1H); 7.38 (t, 2H, J = 8.79 Hz);acid methylamide 7.30 (s, 1H); 6.03 (q, 1H, J = 6.45 Hz); 3.26 (s, 3H);3.09 (s, 3H); 2.82 (d, 3H, J = 4.69 Hz); 1.76 (d, 3H, J = 6.45) 409.6-(3,5-Dimethyl- ¹H NMR in DMSO: (M + H)⁺ = 476 A <1isoxazol-4-yl)-2-(4- 8.41 (brd, 1H, J = 4.69); 7.95 (m,fluoro-phenyl)-5-(5- 2H); 7.62 (s, 1H); 7.40 (m, 3H); methyl-isoxazol-3-6.16 (s, 1H); 5.20 (s, 2H); ylmethoxy)-benzofuran- 2.86 (d, 3H, J = 4.69Hz); 2.41 (s, 3H); 3-carboxylic acid 2.28 (s, 3H); 2.10 (s, 3H)methylamide 410. 6-(3,5-Dimethyl- ¹H NMR in DMSO: (M + H)⁺ = 478 A <1isoxazol-4-yl)-2-(4- 8.41 (brd, 1H, J = 4.10 Hz); fluoro-phenyl)-5- 7.95(m, 2H); 7.83 (d, 1H, (thiazol-2-ylmethoxy)- J = 2.34 Hz); 7.75 (d, 1H,benzofuran-3-carboxylic J = 2.93 Hz); 7.64 (s, 1H); 7.46 (s, acidmethylamide 1H); 7.38 (t, 2H, J = 8.79 Hz); 5.49 (s, 2H); 2.86 (d, 3H, J= 4.10 Hz); 2.30 (s, 3H); 2.12 (s, 3H) 411. 6-Acetyl-2-(4-fluoro- ¹H NMRin CD₃OD: (M + H)⁺ = 312 B *** phenyl)-benzofuran-3- 8.22 (m, 1H); 7.98(m, 3H); carboxylic acid 7.76 (m, 1H); 7.27 (m, 2H); 2.96 (s,methylamide 3H); 2.67 (s, 3H) 412. 2-(4-Fluoro-phenyl)-5- ¹H NMR inDMSO: (M + H)⁻ = 463 A *** (2-hydroxy-2-methyl- 8.41 (brm, 1H); 7.94 (m,2H); propoxy)-6- 7.64 (s, 1H); 7.38 (t, 2H, (methanesulfonyl- J = 8.79Hz); 7.20 (s, 1H); 4.61 (s, methyl-amino)- 1H); 3.86 (s, 2H); 3.24 (s,3H); benzofuran-3-carboxylic 3.08 (s, 3H); 2.83 (d, 3H, acid methylamideJ = 4.69 Hz); 1.28 (s, 6H) 413. 5- ¹H NMR in DMSO: (M + H)⁺ = 506 A ***Diethylcarbamoylmethoxy- 8.42 (brd, 1H, J = 4.69 Hz);2-(4-fluoro-phenyl)-6- 7.93 (m, 2H); 7.60 (s, 1H); 7.38 (t,(methanesulfonyl- 2H, J = 8.79 Hz); 7.10 (s, 1H); methyl-amino)- 4.98(s, 2H); 3.36 (m, 4H); benzofuran-3-carboxylic 3.27 (s, 3H); 3.09 (s,3H); 2.81 (d, acid methylamide 3H, J = 4.69 Hz); 1.21 (t, 3H, J = 7.03Hz); 1.06 (t, 3H, J = 7.03) 414. 6-(3,5-Dimethyl- ¹H NMR in DMSO: (M +H)⁺ = 409.0 A *** isoxazol-4-yl)-5-ethoxy- 8.41-8.42 (d, 1H, J = 4.69Hz); 2-(4-fluoro-phenyl)- 7.92-7.97 (m, 2H); 7.58 (s, 1H);benzofuran-3-carboxylic 7.35-7.41 (t, 2H, J = 8.79 Hz); acid methylamide7.21 (s, 1H); 4.05-4.12 (q, 2H, J = 7.03 Hz); 2.84-2.85 (d, 3H, J = 4.69Hz); 2.30 (s, 3H); 2.12 (s, 3H); 1.27-1.32 (t, 3H, J = 7.03 Hz) 415.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M − H)⁻ = 531 A <1(methanesulfonyl- 12.30 (brs, 1H); 8.41 (brd, 1H, methyl-amino)-5- J =4.69 Hz); 7.92 (m, 2H); (thiazol-2- 7.67 (s, 1H); 7.51 (d, 1H, J = 3.52Hz); ylcarbamoylmethoxy)- 7.38 (t, 2H, J = 8.79 Hz); 7.27 (d,benzofuran-3-carboxylic 1H, J = 3.52 Hz); 7.18 (s, 1H); acid methylamide5.06 (s, 2H); 3.12 (m, 6H); 2.79 (d, 3H, J = 4.69 Hz) 416.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M − H)⁻ = 532 A <1(methanesulfonyl- 12.81 (brs, 1H), 9.22 (s, 1H); methyl-amino)-5- 8.42(brm, 1H); 7.92 (m, 2H); ([1,3,4]thiadiazol-2- 7.67 (s, 1H); 7.39 (t,2H, ylcarbamoylmethoxy)- J = 8.79 Hz); 7.18 (s, 1H); 5.12 (s,benzofuran-3-carboxylic 2H); 3.17 (s, 3H); 3.10 (s, 3H); acidmethylamide 2.79 (d, 3H, J = 4.10 Hz) 417. 5-[(4,5-Dimethyl-thiazol- ¹HNMR in DMSO: (M + H)⁺ = 561 A <1 2-ylcarbamoyl)- 12.05 (brs, 1H); 8.41(brd, 1H, methoxy]-2-(4-fluoro- J = 4.10 Hz); 7.92 (m, 2H); phenyl)-6-7.66 (s, 1H); 7.39 (t, 2H, J = 8.79 Hz); (methanesulfonyl- 7.16 (s, 1H);5.00 (s, 2H); methyl-amino)- 3.28 (s, 3H); 3.10 (s, 3H); 2.80 (d,benzofuran-3-carboxylic 3H, J = 4.10 Hz); 2.24 (s, 3H); acid methylamide2.17 (s, 3H) 418. 5-Cyclopropyl-2-(4- ¹H NMR in DMSO: (M + H)⁺ = 403 A<1 fluoro-phenyl)-6- 9.32 (brs, 1H); 8.36 (m, 1H); methanesulfonylamino-7.94 (dd, J = 5.3 & 8.8 Hz, 2H); benzofuran-3-carboxylic 7.58 (s, 1H);7.36 (t, J = 8.8 Hz, acid methylamide 2H); 7.14 (s, 1H); 3.03 (s, 3H);2.83 (d, J = 4.6 Hz, 3H); 2.31 (m, 1H); 1.00 (m, 2H); 0.68 (m, 2H) 419.5-[2-(4-Cyano-piperidin- ¹H NMR in DMSO: (M + H)⁺ = 517.1 A <11-yl)-ethoxy]-6-(3,5- 8.41-8.43 (d, 1H, J = 4.69 Hz);dimethyl-isoxazol-4-yl)- 7.93-7.97 (m, 2H); 7.58 (s, 1H);2-(4-fluoro-phenyl)- 7.35-7.41 (t, 2H, J = 8.79 Hz);benzofuran-3-carboxylic 7.26 (s, 1H); 4.08-4.12 (t, 2H, acid methylamideJ = 5.86 Hz); 2.85-2.86 (d, 3H, J = 4.69 Hz); 2.82-2.86 (m, 1H);2.63-2.66 (t, 2H, J = 5.86 Hz); 2.50-2.55 (m, 3H); 2.31 (s, 3H);2.26-2.31 (m, 1H); 2.14 (s, 3H); 1.77-1.84 (m, 2H); 1.63-1.70 (m, 2H)420. 2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M − H)⁻ = 443 A <1methanesulfonylamino-5- 9.29 (s, 1H); 8.48 (d, J = 4.84 Hz,thiophen-2-yl- 1H); 8.02-7.97 (m, 2H); 7.75 (s, benzofuran-3-carboxylic1H); 7.97 (s, 1H); 7.64 (d, acid methylamide J = 5.27 Hz, 1H); 7.45-7.37(m, 3H); 7.19-7.16 (m, 1H); 2.94 (s, 3H); 2.84 (d, J = 4.40 Hz, 3H) 421.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 464 A <1(methanesulfonyl- 8.40 (brd, 1H, J = 4.69 Hz); methyl-amino)-5- 7.93 (m,3H); 7.70 (s, 1H); 7.39 (t, methylcarbamoylmethoxy- 2H, J = 8.79 Hz);7.16 (s, 1H); benzofuran-3- 4.66 (s, 2H); 3.25 (s, 3H); carboxylic acid3.13 (s, 3H); 2.83 (d, 3H, J = 4.69 Hz); methylamide 2.68 (d, 3H, J =4.69 Hz) 422. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M − H)⁻ = 545 B<10 (1-hydroxymethyl- 8.53 (d, J = 4.8 Hz, 1H); 8.07 (dd,cyclopropylmethoxy)-6- J = 8.8, 5.3 Hz, 2H); 7.72 (s, 2H);[(1-hydroxymethyl- 7.52 (t, J = 8.8 Hz, 2H); 4.50 (brd,cyclopropylmethyl)- 1H); 4.15 (t, J = 9.3 Hz, 1H);methanesulfonyl-amino]- 4.07 (d, J = 9.9 Hz, 1H); 3.60 (m, 2H);benzofuran-3-carboxylic 3.50 (m, 1H); 3.30 (d, J = 11.0 Hz, acidmethylamide 1H); 3.17 (s, 3H); 2.94 (d, J = 4.8 Hz, 3H); 0.75 (s, 4H)423. 6-Diethylamino-5- ¹H NMR in CDCl₃: (M + H)⁺ = 385 A <1ethoxy-2-(4-fluoro- 7.85 (dd, J = 8.8, 5.3 Hz, 2H);phenyl)-benzofuran-3- 7.30 (s, 1H); 7.77 (t, J = 8.8 Hz, carboxylic acid2H); 6.67 (s, 1H); 5.75 (brs, methylamide 1H); 4.10 (q, J = 7.0 Hz, 2H);3.20 (q, J = 7.0 Hz, 4H); 1.40 (t, J = 7.0 Hz, 6H); 1.30 (t, J = 7.0 Hz,3H) 424. 5-Carbamoylmethoxy-2- ¹H NMR in DMSO: (M − H)⁻ = 448 A <1(4-fluoro-phenyl)-6- 8.41 (brd, 1H, J = 4.69 Hz); (methanesulfonyl- 7.93(m, 2H), 7.72 (s, 1H), 7.40 (m, methyl-amino)- 4H); 7.15 (s, 1H); 4.64(s, 2H); benzofuran-3-carboxylic 3.26 (s, 3H); 3.13 (s, 3H); acidmethylamide 2.84 (d, 3H, J = 4.69 Hz) 425. 5-[2-(3,5-Dimethyl- ¹H NMR inDMSO: (M + H)⁺ = 515 A <1 pyrazol-1-yl)-ethoxy]-2- 8.41 (brd, 1H, J =4.69 Hz); (4-fluoro-phenyl)-6- 7.94 (m, 2H); 7.60 (s, 1H); 7.38 (t,(methanesulfonyl- 2H, J = 8.79 Hz); 7.22 (s, 1H); methyl-amino)- 5.81(s, 1H); 4.44 (brd, 2H, benzofuran-3-carboxylic J = 4.69 Hz); 4.40 (brd,2H, acid methylamide J = 4.69 Hz); 3.06 (s, 3H); 2.89 (s, 3H); 2.84 (d,3H, J = 4.69 Hz); 2.28 (s, 3H); 2.08 (s, 3H) 426. 2-(4-Fluoro-phenyl)-5-¹H NMR in DMSO: (M − H)⁻ = 427.0 A <1 furan-2-yl-6- 9.34 (s, 1H); 8.50(d, J = 4.40 Hz, methanesulfonylamino- 2H); 7.99-7.96 (m, 2H); 7.91 (s,benzofuran-3-carboxylic 1H); 7.82 (s, 1H); 7.74 (s, 1H); acidmethylamide 7.40 (t, J = 8.79 Hz, 2H); 7.09 (d, J = 3.52 Hz, 1H); 6.65(s, 1H); 3.04 (s, 3H); 2.85 (d, J = 4.40 Hz, 3H) 427. 6-(3,5-Dimethyl-¹H NMR in DMSO: (M + H)⁺ = 477 A <1 isoxazol-4-yl)-2-(4- 8.44-8.45 (d,1H, J = 4.69 Hz); fluoro-phenyl)-5-(1- 7.93-7.97 (m, 2H); 7.63 (s, 1H);methyl-1H-tetrazol-5- 7.53 (s, 1H); 7.36-7.42 (t, 2H,ylmethoxy)-benzofuran- J = 8.79 Hz); 5.56 (s, 2H); 3.93 (s, 3-carboxylicacid 3H); 2.86-2.88 (d, 3H, methylamide J = 4.69 Hz); 2.24 (s, 3H); 2.07(s, 3H) 428. 5-Cyclopropylmethoxy- ¹H NMR in DMSO: (M + H)⁺ = 435 A <16-(3,5-dimethyl-isoxazol- 8.39-8.41 (d, 1H, J = 4.69 Hz);4-yl)-2-(4-fluoro- 7.91-7.96 (m, 2H); 7.58 (s, 1H);phenyl)-benzofuran-3- 7.35-7.41 (t, 2H, J = 8.79 Hz); carboxylic acid7.18 (s, 1H); 3.86-3.88 (d, 2H, methylamide J = 7.03 Hz); 2.83-2.85 (d,3H, J = 4.69 Hz); 2.32 (s, 3H); 2.15 (s, 3H); 1.12-1.20 (m, 1H);0.51-0.57 (m, 2H); 0.26-0.31 (m, 2H) 429. 6-(3,5-Dimethyl- ¹H NMR inDMSO: (M + H)⁺ = 490 A <1 isoxazol-4-yl)-5-(3,5- 8.43-8.45 (d, 1H, J =4.69 Hz); dimethyl-isoxazol-4- 7.92-7.96 (m, 2H); 7.59 (s, 1H);ylmethoxy)-2-(4-fluoro- 7.44 (s, 1H); 7.36-7.41 (t, 2H,phenyl)-benzofuran-3- J = 8.79 Hz); 4.97 (s, 2H); carboxylic acid2.86-2.87 (d, 3H, J = 4.69 Hz); 2.28 (s, methylamide 3H); 2.21 (s, 3H);2.03 (s, 3H); 1.97 (s, 3H) 430. 2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃:(M + H)⁺ = 381 A <10 methoxy-6-(5-methyl- 8.05 (s, 1H); 7.92-7.87 (m,2H); [1,3,4]oxadiazol-2-yl)- 7.52 (s, 1H); 7.27-7.23 (m, 2H);benzofuran-3-carboxylic 5.80 (s, 1H); 4.03 (s, 3H); acid methylamide3.02 (d, J = 4.5 Hz, 3H); 2.65 (s, 3H) 431. 6-(3-Cyano-4-hydroxy-2- ¹HNMR in DMSO: (M + H)⁺ = 436 A *** oxo-2,5-dihydro-pyrrol- 8.36-8.34 (m,1H); 1-ylmethyl)-2-(4-fluoro- 7.94-7.89 (m, 2H); 7.36-7.28 (m, 3H);phenyl)-5-methoxy- 7.10 (s, 1H); 4.47 (s, 2H); benzofuran-3-carboxylic3.85 (s, 2H); 2.81 (d, J = 4.2 Hz, 3H) acid methylamide 432.4-Chloro-6-[ethyl-(2- ¹H NMR in CDCl₃: (M + H)⁺ = 343 B <10methoxy-acetyl)-amino]- 7.90 (dd, J = 8.3, 5.3 Hz, 2H);2-(4-fluoro-phenyl)-5- 7.40 (s, 1H); 7.20 (t, J = 8.3 Hz,methoxy-benzofuran-3- 2H); 5.90 (brs, 1H); 3.91 (s, carboxylic acid 3H);3.80-3.70 (m, 2H); 3.62 (s, methylamide 2H); 3.30 (s, 3H); 2.98 (d, J =4.4 Hz, 3H); 1.10 (t, J = 7.0 Hz, 3H) 433. 6-(3,5-Dimethyl- ¹H NMR inDMSO: (M + H)⁺ = 494 A *** isoxazol-4-yl)-2-(4- 8.41-8.42 (d, 1H, J =4.69 Hz); fluoro-phenyl)-5-(2- 7.93-7.97 (m, 2H); 7.58 (s, 1H);morpholin-4-yl-ethoxy)- 7.35-7.41 (t, 2H, J = 8.79 Hz);benzofuran-3-carboxylic 7.26 (s, 1H); 4.11-4.14 (t, 2H, acid methylamideJ = 5.28 Hz); 3.52-3.55 (t, 4H, J = 4.10 Hz); 2.84-2.86 (d, 3H, J- 4.69Hz); 2.61-2.65 (t, 2H, J = 5.86 Hz); 2.36-2.40 (t, 4H, J = 4.10 Hz);2.31 (s, 3H); 2.15 (s, 3H) 434. 6-(3,5-Dimethyl- ¹H NMR in DMSO: (M +H)⁺ = 506.1 B *** isoxazol-4-yl)-2-(4- 8.42-8.44 (d, 1H, J = 4.69 Hz);fluoro-phenyl)-5-(3- 7.92-7.97 (m, 2H); 7.58 (s, 1H);piperidin-1-yl-propoxy)- 7.35-7.41 (t, 2H, J = 8.79 Hz);benzofuran-3-carboxylic 7.22 (s, 1H); 4.01-4.06 (t, 2H, acid methylamideJ = 6.45 Hz); 2.84-2.85 (d, 3H, J = 4.69 Hz); 2.28 (s, 3H); 2.25-2.28(m, 4H); 2.11 (s, 3H); 1.91 (s, 2H); 1.75-1.84 (m, 2H); 1.36-1.48 (m,4H); 0.84-0.86 (m, 2H) 435. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M +H)⁺ = 383.0 B >30 (thiazol-4-ylmethoxy)- 9.12 (s, 1H); 8.34 (d, J = 4.0Hz, benzofuran-3-carboxylic 1H); 7.92 (m, 2H); 7.79 (s, 1H); acidmethylamide 7.57 (d, J = 8.8 Hz, 1H); 7.34 (t, J = 8.3 Hz, 2H); 7.23 (s,1H); 7.07 (m, 1H); 5.25 (s, 2H); 2.82 (d, J = 3.5 Hz, 3H) 436.2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ = 358.1 A <10(2-hydroxy-acetyl)-5- 8.20 (s, 1H); 7.87 (m, 2H); methoxy-benzofuran-3-7.45 (s, 1H); 7.22 (m, 2H); 5.77 (brs, carboxylic acid 1H); 4.82 (s,2H); 4.01 (s, 3H); methylamide 3.75 (brs, 1H); 3.00 (d, J = 4.8 Hz, 3H)437. 5-Cyclopropyl-2-(4- ¹H NMR in DMSO: (M + H)⁺ = 417 A <1fluoro-phenyl)-6- 8.39 (d, J = 4.40 Hz, 1H); (methanesulfonyl- 7.95-7.90(m, 2H); 7.81 (s, 1H); methyl-amino)- 7.39-7.33 (m, 2H); 7.13 (s, 1H);benzofuran-3-carboxylic 3.22 (s, 3H); 3.14 (s, 3H); 2.82 (d, acidmethylamide J = 4.40 Hz, 3H); 2.33-2.24 (m, 1H); 0.96 (d, J = 8.35 Hz,2H); 0.79-0.63 (m, 2H) 438. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M −H)⁻ = 435 A *** hydroxy-6-[(2-hydroxy- 9.97 (s, 1H); 8.40 (brd, 1H,propyl)-methanesulfonyl- J = 4.10 Hz); 7.92 (m, 2H);amino]-benzofuran-3- 7.55 (s, 1H); 7.35 (t, 2H, J = 8.79 Hz); carboxylicacid 7.09 (s, 1H); 4.72 (brs, 1H); methylamide 3.58-3.40 (m, 3H); 3.01(s, 3H); 2.80 (d, 3H, J = 4.69 Hz); 1.03 (d, 3H, J = 5.86 Hz) 439.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M − H)⁻ = 449 A ***[(2-hydroxy-propyl)- 8.41 (brd, 1H, J = 5.28 Hz);methanesulfonyl-amino]- 7.92 (m, 2H); 7.66 (s, 1H); 7.36 (t,5-methoxy-benzofuran-3- 2H, J = 8.79 Hz); 7.18 (s, 1H); carboxylic acid4.66 (brs, 1H); 3.89 (s, 3H); methylamide 3.56 (brm, 3H); 3.00 (s, 3H);2.82 (d, 3H, J = 4.69 Hz); 1.03 (d, 3H, J = 5.28 Hz) 440.6-(1-Acetyl-pyrrolidin-2- ¹H NMR in CDCl₃: (M + H)⁺ = 409.1 A ***yl)-5-ethyl-2-(4-fluoro- (mixture of two enantiomers)phenyl)-benzofuran-3- 7.90 (m, 2H); 7.68 (s, 1H); carboxylic acid 7.21(s, 1H); 7.15 (m, 2H); methylamide 5.80 (brs, 1H); 5.20 (dd, J = 2.1 Hz,J = 8.4 Hz, 1H); 3.85 (m, 1H); 3.65 (m, 1H); 3.20-3.40 (1H); 3.01 (d, J= 5.2 Hz, 3H); 2.70-2.90, 2H); 2.30-2.50, 1H); 1.80-2.10, 2H); 1.82 (s,3H); 1.34 (t, J = 7.5 Hz, 3H) 441. 2-(4-Fluoro-phenyl)-6- ¹H NMR inDMSO: (M − H)⁻ = 431.0 A <1 methanesulfonylamino-5- 9.15 (s, 1H); 8.44(d, J = 4.40 Hz, (tetrahydro-furan-2-yl)- 1H); 7.94-7.89 (m, 2H); 7.62(d, benzofuran-3-carboxylic J = 4.40 Hz, 2H); 7.39-7.34 (m, acidmethylamide 2H); 5.21 (t, J = 7.47 Hz, 1H); 4.06-4.03 (m, 1H); 3.82-3.80(m, 1H); 3.08 (s, 3H); 2.82 (d, J = 4.40 Hz, 3H); 2.45-2.41 (m, 1H);1.98-1.94 (m, 2H); 1.65 (m, 1H) 442. 2-(4-Fluoro-phenyl)-5- ¹H NMR inDMSO: (M + H)⁺ = 370.0 A <1 methoxy-6-(tetrahydro- 8.34-8.36 (d, 1H, J =4.69 Hz); furan-3-yl)-benzofuran- 7.90-7.95 (m, 2H); 7.53 (s, 1H);3-carboxylic acid 7.33-7.39 (t, 2H, J = 8.79 Hz); methylamide 7.10 (s,1H); 4.00-4.06 (t, 1H, J = 7.62 Hz); 3.90-3.97 (m, 1H); 3.89 (s, 3H);3.68-3.85 (m, 2H); 3.56-3.61 (t, 1H, J = 7.62 Hz); 2.83-2.84 (d, 3H, J =4.69 Hz); 2.21-2.31 (m, 1H); 1.95-2.06 (m, 1H) 443.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 465 A <1(methanesulfonyl- 8.40 (d, J = 4.2 Hz, 1H); methoxymethyl-amino)- 7.94(dd, J = 8.8, 5.3 Hz, 2H); 7.65 (s, 5-propoxy-benzofuran-3- 1H); 7.36(t, J = 8.8 Hz, 2H); carboxylic acid 7.19 (s, 1H); 5.94 (brs, 2H); 4.03(t, methylamide J = 7.0 Hz, 2H); 3.32 (s, 3H); 3.08 (s, 3H); 2.81 (d, J= 4.2 Hz, 3H); 1.80 (sextet, J = 7.0 Hz, 2H); 1.01 (t, J = 7.0 Hz, 3H)444. 2-(4-Fluoro-phenyl)-5- ¹H NMR in DMSO: (M − H)⁻ = 421 A <10hydroxy-6- 10.08 (s, 1H); 8.40 (d, J = 4.4 Hz, (methanesulfonyl- 1H);7.92 (dd, J = 8.8, 5.7 Hz, methoxymethyl-amino)- 2H); 7.53 (s, 1H); 7.35(t, benzofuran-3-carboxylic J = 8.8 Hz, 2H); 7.12 (s, 1H); acidmethylamide 4.92 (brs, 2H); 3.31 (s, 3H); 3.08 (s, 3H); 2.80 (d, J = 4.8Hz, 3H) 445. 2-(4-Fluoro-phenyl)-6- ¹H NMR in CDCl₃: (M + H)⁺ = 421 A <1methanesulfonylamino-5- 7.82 (dd, J = 8.8 & 6.3 Hz, 2H);propoxy-benzofuran-3- 7.73 (s, 1H); 7.41 (s, 1H); carboxylic acid 7.18(t, J = 8.8 Hz, 2H); 6.92 (s, 1H); methylamide 5.77 (brs, 1H); 4.07 (t,J = 6.6 Hz, 2H); 2.98 (d, J = 9.8 Hz, 3H); 2.95 (s, 3H); 1.85 (sextet, J= 7.0 Hz, 2H); 1.06 (t, J = 7.0 Hz, 3H) 446. 5-(4-Cyano-benzyloxy)- ¹HNMR in DMSO: (M − H)⁻ = 536 A <1 2-(4-fluoro-phenyl)-6- 8.40 (d, J = 4.6Hz, 1H); (methanesulfonyl- 7.93 (dd, J = 8.8, 5.3 Hz, 2H); 7.88 (d,methoxymethyl-amino)- J = 8.2 Hz, 2H); 7.75 (s, 1H);benzofuran-3-carboxylic 7.71 (d, J = 8.2 Hz, 2H); 7.37 (t, acidmethylamide J = 8.8 Hz, 2H); 7.31 (s, 1H); 5.33 (s, 2H); 4.94 (brs, 2H);3.31 (s, 3H); 3.04 (s, 3H); 2.81 (d, J = 4.6 Hz, 3H) 447.5-(3-Cyano-benzyloxy)- ¹H NMR in DMSO: (M + H)⁺ = 536 A <12-(4-fluoro-phenyl)-6- 8.40 (d, J = 4.4 Hz, 1H); 8.00 (s,(methanesulfonyl- 1H); 7.90-7.80 (m, 4H); 7.75 (s, methoxymethyl-amino)-1H); 7.62 (t, J = 8.0 Hz, 1H); benzofuran-3-carboxylic 7.39 (t, J = 8.0Hz, 2H); 7.31 (s, 1H); acid methylamide 5.28 (s, 2H); 4.92 (brs, 2H);3.31 (s, 3H); 3.04 (s, 3H); 2.82 (d, J = 4.4 Hz, 3H) 448. 6-(1- ¹H NMRin CDCl₃: (M + H)⁺ = 465 A *** Cyclopropanecarbonyl- 7.84 (m, 2H); 7.34(s, 1H); pyrrolidin-2-yl)-2-(4- 7.18-7.23 (m, 3H); 5.74 (brs, 1H);fluoro-phenyl)-5- 5.50 (d, J = 7.47 Hz, 1H); isopropoxy-benzofuran- 4.73(septet, J = 5.72 Hz, 1H); 3.85 (m, 3-carboxylic acid 1H); 3.82 (m, 1H);2.99 (d, methylamide J = 4.84 Hz, 3H); 2.22-2.43 (m, 1H); 1.92-2.00 (m,2H); 1.79-1.80 (m, 2H); 1.40 (m, 6H); 0.85-1.01 (m, 4H) 449.2-(4-Fluoro-phenyl)-5- ¹H NMR in CDCl₃: (M + H)⁺ = 368 A *** methoxy-6-8.51 (s, 1H); 8.11 (s, 1H); [1,3,4]oxadiazol-2-yl- 7.91-7.87 (m, 2H);7.54 (s, 1H); benzofuran-3-carboxylic 7.26-7.20 (m, 2H); 5.80 (s, 1H);acid methylamide 4.04 (s, 3H); 2.99 (d, J = 5.4 Hz, 3H) 450.2-(4-Fluoro-phenyl)-6- ¹H NMR in DMSO: (M + H)⁺ = 458.9 A ***(methanesulfonyl- 8.48 (m, 1H); 7.98-7.96 (m, methyl-amino)-5- 3H); 7.83(m, 1H); thiophen-2-yl- 7.61-7.60 (m, 1H); 7.42-7.36 (m, 3H);benzofuran-3-carboxylic 7.13 (m, 1H); 3.16 (s, 3H); acid methylamide3.08 (s, 3H); 2.66 (d, J = 3.96 Hz, 3H) 451. 2-(4-Fluoro-phenyl)-6- ¹HNMR in DMSO: (M − H)⁻ = 515 A *** {[2-(4-fluoro-phenyl)-2- 10.03 (brs,1H); 8.42 (brd, 1H, hydroxy-ethyl]- J = 4.69 Hz); 7.94 (m, 2H);methanesulfonyl-amino}- 7.38 (t, 2H, J = 8.79 Hz); 7.32 (m, 3H);5-hydroxy-benzofuran-3- 7.13 (m, 3H); 5.58 (m, 1H); carboxylic acid 4.62(m, 1H); 3.70 (brm, 2H); 3.01 (s, methylamide 3H); 2.82 (d, 3H, J = 4.10Hz) 452. 5-Methoxy-2-phenyl- *** *** A <10 benzofuran-3-carboxylic acidmethylamide 453. 5-Hydroxy-2-phenyl- *** *** C ***benzofuran-3-carboxylic acid methylamide *All ¹H NMR and ¹³C NMR spectrawere acquired on a Varian Mercury VX 300 Spectrometer and referenced totetramethylsilane (TMS) unless indicated otherwise. Chemical shifts andcoupling constants are reported in parts per million (ppm) and Hertz (Hz) respectively. Multiplicities indicated are: s = singlet, d =doublet, t = triplet, q = quartet, m = multiplet dd = doublet ofdoublets, and br indicates a broad signal. **Mass Spectroscopy data isexpressed as a mass to charge ratio (m/z) for either (M + H) or (M − H)molecular ion. *** Indicates that data was not collected.

Table 2 lists examples of pharmaceutically acceptable salts of selectcompounds listed in Table 1.

TABLE 2 Example Number Name NMR Data* 454.2-(4-Fluoro-phenyl)-5-isopropoxy-6- ¹H NMR in DMSOmethanesulfonylamino-benzofuran-3-carboxylic 8.18-8.15 (br m, 1H);7.87-7.81 (m, 2H); acid methylamide, potassium salt 7.28-7.22 (m, 2H);6.77 (s, 1H); 4.57 (septet, J = 6.45 Hz, 1H); 2.78 (d, J = 4.7 Hz, 3H);2.55 (s, 3H); 1.18 (d, J = 5.86 Hz, 6H) 455.2-(4-Fluoro-phenyl)-5-isopropoxy-6- ¹H NMR in DMSOmethanesulfonylamino-benzofuran-3-carboxylic 8.18-8.15 (br m, 1H);7.87-7.81 (m, 2H); acid methylamide, sodium salt 7.28-7.22 (m, 2H); 6.77(s, 1H); 4.57 (septet, J = 6.45 Hz, 1H); 2.78 (d, J = 4.7 Hz, 3H); 2.55(s, 3H); 1.18 (d, J = 5.86 Hz, 6H) 456.2-(4-Fluoro-phenyl)-6-methanesulfonylamino-5- ***methoxy-benzofuran-3-carboxylic acid methylamide, potassium salt 457.2-(4-Fluoro-phenyl)-6-methanesulfonylamino-5- ***methoxy-benzofuran-3-carboxylic acid methylamide, sodium salt 458.2-(4-Fluoro-phenyl)-5-isopropoxy-6-(propane-2- ***sulfonylamino)-benzofuran-3-carboxylic acid methylamide, potassium salt459. 2-(4-Fluoro-phenyl)-5-isopropoxy-6-(propane-2- ***sulfonylamino)-benzofuran-3-carboxylic acid methylamide, sodium salt460. 2-(4-Fluoro-phenyl)-5-isopropoxy-6- ***methanesulfonylamino-benzofuran-3-carboxylic acid isopropylamide,potassium salt 461. 2-(4-Fluoro-phenyl)-5-isopropoxy-6- ***methanesulfonylamino-benzofuran-3-carboxylic acid isopropylamide, sodiumsalt 462. 2-(4-Fluoro-phenyl)-5-isopropoxy-6- ***methanesulfonylamino-benzofuran-3-carboxylic acid ethylamide, potassiumsalt 463. 2-(4-Fluoro-phenyl)-5-isopropoxy-6- ***methanesulfonylamino-benzofuran-3-carboxylic acid ethylamide, sodiumsalt *All ¹H NMR and ¹³C NMR spectra were acquired on a Varian MercuryVX 300 Spectrometer and referenced to tetramethylsilane (TMS) unlessindicated otherwise. Chemical shifts and coupling constants are reportedin parts per million (ppm) and Hertz (Hz) respectively. Multiplicitiesindicated are: s = singlet, d = doublet, t = triplet, q = quartet, m =multiplet dd = doublet of doublets, and br indicates a broad signal. ***Indicates that data was not collected.

Example 464 Inhibition of Viral RNA Replication

Antiviral activity of representative compounds of the invention wasfirst evaluated in a human liver-derived cell line (Huh-7-Clone A)containing the HCV replicon (BB7 sequence) (See Lohmann et al. Science.1999, 285:110-3; Blight K J et al., Science. 2000, 290:1972-4;Pietschmann, T. et al., J. Virol. 2001, 73:1252-1264; and Lohmann, V. etal., J. Virol. 2001, 75:1437-1449). The HCV replicon is a subgenomicviral RNA that expresses the HCV proteins required for its ownreplication. These proteins include non-structural proteins NS3, NS4A,NS4B, NS5A and NS5B. The replicon also contains a foreign gene encodinga drug-selectable marker (neomycin phosphotransferase) to allow for G418(neomycin) selection of cells that contain the replicon.

An ELISA (enzyme-linked immunosorbant assay) was used to determine theeffect of compounds within the scope of the invention on the amount ofHCV NS5A protein produced after a 72-hour incubation of thereplicon-containing cells in the presence of varying concentrations ofcompound. COSTAR® 96-well cell culture plates were used but other knowncell culture plates may be used. After incubation, media is removed fromwells and the cells are fixed to the assay plate using 0.05%glutaraldehyde. The glutaraldehyde is then washed off usingphosphate-buffered saline (PBS) following a 1 hour incubation and cellsare blocked for non-specific antibody binding using for exampleSUPERBLOCK® reagent (blocking buffer) in PBS. The blocking agent isrinsed from the cells with PBS after 1 hour at 37° C. and primarymonoclonal antibody is added to each well containing compound. Primaryantibody is incubated for 1 hour at 37° C. and rinsed 3 times with PBScontaining 0.02% TWEEN-20™ before addition of Horseradish Peroxidase(HRP) conjugated secondary antibody. HRP is incubated for 1 hour at 37°C. and rinsed several times, first with PBS/TWEEN-20™ followed by PBSalone. To quantify peroxidase activity, 3,3′,5,5′-tetramethylbenzidine(TMB) substrate is added to the plate and after 30 minutes, the platesare read in an ELISA plate reader at an OD of 650 nm. Compound doseresponse was measured in an 8-point dose curve diluted serially todetermine the inhibitory concentration at 50% (EC₅₀ value).Representative compounds of the invention showed a dose-dependentinhibition of intracellular NS5A levels. Ranges of 50% effectiveconcentrations (EC₅₀s) for representative compounds within the scope ofthis invention are listed in Table 1. Preferred compounds have 50%effective concentrations at about 30 μM or less, more preferredcompounds have 50% effective concentrations at about 5 μM or less, andmost preferred compounds have 50% effective concentrations at about 0.5μM or less.

Example 465 Inhibition of Viral RNA-Dependent RNA Polymerase (RdRp)

The HCV NS5B-directed RdRp activity was established and characterized ina standard in vitro biochemical assay using a purified HCV NS5B proteinderived from the consensus sequence of a patient infected with HCVgenotype 1b virus (BB7). (See Blight K J et al., Science. 2000,290:1972-4). The NS5B consensus sequence was cloned and expressed in E.coli as a histidine tagged (GSHHHHHH) fusion protein, of which thecarboxyl terminal 21 amino acids were removed to enhance its solubility.

In addition to evaluating their activity in the replicon assay,representative compounds within the scope of the present invention, asshown in examples 1-453 of Table 1, were also evaluated for antiviralactivity using this assay. A measure of the inhibitory activity ofcompounds of the invention may be expressed as IC₅₀ values. IC₅₀ valuesrepresent the concentration of the compound at which 50% of the RdRpactivity is inhibited. The results of the assay for inhibition of RdRpactivity of HCV, NS5B proteins for a substantial majority of thecompounds tested revealed IC₅₀ values ranging from <0.5 to about 30 μM.These low concentrations of test compounds required to achieve 50%inhibition of the RdRp activity indicate that the compounds of theinvention are effective at inhibiting RNA synthesis by viral RdRpenzymes.

Although the present invention has been described and exemplified interms of certain preferred embodiments, other embodiments will beapparent to those skilled in the art. The invention is, therefore, notlimited to the particular embodiments described and exemplified, but iscapable of modification or variation without departing from the spiritof the invention, the full scope of which is delineated by the appendedclaims.

1. A compound having the formula:

wherein: R₁ represents a radical selected from the group consisting ofhydrogen, alkyl, halogen, and cyano; R₂ represents a radical selectedfrom the group consisting of hydrogen, a substituted or unsubstitutedalkyl radical, a substituted or unsubstituted alkoxy group, hydroxy,cycloalkyl, cycloalkyloxy, polyfluoroalkyl, polyfluoroalkoxy, halogen,amino, monoalkylamino, dialkylamino, cyano, a substituted orunsubstituted benzyloxy group, and a substituted or unsubstitutedheterocyclic radical; R₃ represents a radical selected from the groupconsisting of hydrogen, a substituted or unsubstituted alkyl radical, asubstituted or unsubstituted alkoxy group, alkenyl, halogen, hydroxy,polyfluoroalkyl, polyfluoroalkoxy, formyl, carboxyl, alkylcarbonyl,alkoxycarbonyl, hydroxyalkylcarbonyl, amino, a substituted orunsubstituted monoalkylamino, dialkylamino, cyano, amido, alkoxyamido, asubstituted or unsubstituted heteroarylamino, acetylsulfonylamino,ureido, carboxamide, sulfonamide, a substituted sulfonamide, asubstituted or unsubstituted heterocyclosulfonyl, alkylthio,alkylsulfinyl, alkylsulfonyl, alkylsulfonic acid, a substituted orunsubstituted heterocyclic radical, and —O(CH₂)—C(═O)—R₇; R₄ representsa radical selected from the group consisting of hydrogen, alkyl,halogen, and alkoxy; R₅ represents a radical selected from the groupconsisting of an alkyl (C₁-C₆) group, cycloalkyl, and cycloalkylalkyl;R₆ represents a radical selected from the group consisting of asubstituted or unsubstituted aryl group and a substituted orunsubstituted heteroaryl group; R₇ represents a radical selected fromthe group consisting of dialkylamino, a substituted or unsubstitutedarylamino, a substituted or unsubstituted heteroarylamino, and asubstituted or unsubstituted aryl group, said monoalkylaminosubstituents being one or more radical(s) independently selected fromthe group consisting of cycloalkyl, hydroxy, alkoxy, and a substitutedor unsubstituted heterocyclic radical; said arylamino substituents andsaid heteroarylamino substituents being one or more radical(s)independently selected from an alkyl group and an alkoxycarbonyl; saidsulfonamide substituents being one or more radical(s) independentlyselected from the group consisting of alkenyl, cycloalkyl, alkoxy,hydroxy, halogen, polyfluoroalkyl, polyfluoroalkoxy, carboxyl,alkylcarbonyl, alkoxycarbonyl, carboxamide, a substituted orunsubstituted aryl group, and a substituted or unsubstitutedheterocyclic radical; said heterocyclosulfonyl substituents being one ormore radical(s) independently selected from the group consisting ofalkoxy and hydroxy; said alkyl radical substituents and said alkoxygroup substituents being one or more radical(s) independently selectedfrom the group consisting of alkenyl, amino, monoalkylamino,dialkylamino, alkoxy, cycloalkyl, hydroxy, carboxyl, halogen, cyano,polyfluoroalkyl, polyfluoroalkoxy, sulfonamide, carboxamide,alkylsulfonyl, alkylcarbonyl, alkoxycarbonyl, mercapto,2,2-dimethyl-4-oxo-4H-benzo[1,3]dioxinyl, a substituted or unsubstitutedaryl group, and a substituted or unsubstituted heterocyclic radical;said heterocyclic radical substituents being one or more radical(s)independently selected from the group consisting of alkyl, amino, amido,monoalkylamino, cycloalkyl-alkylamino, dialkylamino, alkoxy,alkoxyalkyl, hydroxy, hydroxyalkyl, cycloalkyl, cycloalkylalkyl,carboxyl, carboxamide, halogen, haloalkyl, cyano, polyfluoroalkyl,polyfluoroalkoxy, alkylsulfonyl, alkylcarbonyl, cycloalkylcarbonyl,alkoxycarbonyl, mercapto, oxo, a substituted or unsubstituted arylgroup, arylalkyl, and a substituted or unsubstituted heteroaryl group;said heteroaryl group substituents being one or more radical(s)independently selected from the group consisting of alkyl, amino,alkoxy, alkoxyalkyl, hydroxy, hydroxyalkyl, cycloalkyl, carboxyl,carboxamide, halogen, polyfluoroalkyl, polyfluoroalkoxy, alkylsulfonyl,mercapto, and oxo; said benzyloxy group substituents being one or moreradical(s) independently selected from the group consisting of alkyl,alkoxy, polyfluoroalkyl, polyfluoroalkoxy, hydroxy, carboxyl,alkoxycarbonyl, halogen, cyano, alkylsulfonyl, and phenyl; said arylgroup substituents being one or more radical(s) independently selectedfrom the group consisting of alkyl, acetylenyl, alkoxy, hydroxy,halogen, polyfluoroalkyl, polyfluoroalkoxy, cyano, amino,monoalkylamino, dialkylamino, aminoalkyl, alkoxyalkoxy, amido,amidoalkyl, carboxyl, alkylsulfonyl, alkylcarbonyl, alkoxycarbonyl,mercapto, and a heterocyclic radical; and pharmaceutically acceptablesalts thereof; with the proviso that said formula does not include thecompounds selected from the group consisting of5-methoxy-2-phenyl-benzofuran-3-carboxylic acid methylamide and5-hydroxy-2-phenyl-benzofuran-3-carboxylic acid methylamide. 2.-27.(canceled)